CN101420941A

CN101420941A - Use of gpr119 receptor agonists for increasing bone mass and for treating osteoporosis, and combination therapy relating thereto

Info

Publication number: CN101420941A
Application number: CNA2007800126629A
Authority: CN
Inventors: 褚志亮; 詹姆斯·N·伦纳德; 于尔格·莱曼; 罗伯特·M·琼斯
Original assignee: Arena Pharmaceuticals Inc
Current assignee: Arena Pharmaceuticals Inc
Priority date: 2006-04-11
Filing date: 2007-04-10
Publication date: 2009-04-29

Abstract

The present invention relates to the use of GPR119 receptor agonists for treating or preventing a condition characterized by low bone mass, such as osteoporosis, and for increasing bone mass in an individual. The present invention further relates to the use of a GPR119 receptor agonist in combination with a dipeptidyl peptidase IV (DPP-IV) inhibitor for treating or preventing a condition characterized by low bone mass, such as osteoporosis, and for increasing bone mass in an individual. A GPR119 receptor agonist and the combination of a GPR119 receptor agonist and a DPP-IV inhibitor promote bone formation in an individual.

Description

Purposes and its correlation combiner therapy that the GPR119 receptor stimulating agent is used to increase bone mass and is used for the treatment of osteoporosis

Technical field

The present invention relates to the GPR119 receptor stimulating agent is used for the treatment of or prevents to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and be used to increase the purposes of the bone mass of individuality.The combination that the invention still further relates to GPR119 receptor stimulating agent and DPP IV (DPP-IV) inhibitor is used for the treatment of or prevents to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and be used to increase the purposes of the bone mass of individuality.The combination of GPR119 receptor stimulating agent and GPR119 receptor stimulating agent and DPP-IV inhibitor promotes individual bone formation.

Background technology

Following argumentation is planned conveniently to understand the present invention, but does not plan to admit that it is a background technology of the present invention.

A. osteoporosis

Osteoporosis is a kind of disabling condition that is characterised in that the bone mass that causes bone strength to reduce loses and the micro structure of framing structure worsens, and its risk of tending to make the patient stand fragility fractures increases.Osteoporosis is attacked altogether in Europe, Japan and the U.S. and is surpassed 7,005 million peoples, and it only just causes above 2,300,000 example fracture in the Europe and the U.S..In the U.S., at least 25% after the whole menopause of osteoporosis invasion and attack among the white man women, and described ratio is elevated to 70% in being higher than 80 years old women.In surpassing 50 years old women, 1/3rd will suffer from osteoporotic fracture, and it causes considerable society and financial burden to society.Described disease is not limited to the women; Old male also may be attacked.During to the year two thousand fifty, the global incidence rate expection of male's Hip Fracture increases by 310%, and can increase by 240% in the women.The lifelong risk of the combination of the hip that is presented, forearm and spinal fracture is about 40% clinically, and is suitable with cardiovascular disease risk.Therefore osteoporotic fracture causes sizable mortality rate, sickness rate and economic cost.Along with crowd's aging, the number of osteoporotic fracture and its expense will double in the period of following 50 at least, unless develop effective preventative strategies can.(for example referring to Ah 's gram people such as (Atik), clinical orthopaedics and correlational study (Clin Orthop Relat Res) (2006) 443:19-24; Thunder thatch (Raisz), Journal of Clinical Investigation (J Clin Invest) (2005) 115:3318-3325; With World Health Organization (WHO) technical report book series 921 (World Health Organization Technical Report Series921) (2003), osteoporosis prevention and processing (Prevention and Management of Osteoporosis).)

B. glucose-dependent-insulinotropic polypeptide (GIP)

Glucose-dependent-insulinotropic polypeptide (GIP is also referred to as CIP) is a kind of 42 amino acid whose peptide incretin (incretin) hormone that has, and it is to discharge from duodenum endocrine K cell in the back of ingesting.Discharge GIP amount depend on the amount of institute's consumption of glucose largely.Shown that GIP stimulates glucose dependency secretion of insulin in the pancreatic beta cell.GIP mediates its effect by specificity G protein-coupled receptor (being GIPR).

Because GIP contains alanine on 2, so it is the good substrate of dipeptidyl peptidase-4 (DPP-IV) (a kind of enzyme of the GIP of regulation and control degraded).Total length GIP (1-42) changed into bioinactivation GIP (3-42) rapidly in excretory several minutes from intestinal K cell.The inhibitory action that has shown DPP-IV can increase the GIP biological activity.(for example referring to De Luke (Drucker), cellular metabolism (Cell Metab) (2006) 3:153-165; Mai Jingtu people such as (McIntosh), regulation and control peptide (Regul Pept) (2005) 128:159-165; Deacon (Deacon), regulation and control peptide (Regul Pept) (2005) 128:117-124; And Allan people such as (Ahren), endocrinology (Endocrinology) (2005) 146:2055-2059.)。The analysis of total length biological activity GIP (for example in blood) can be used the N-terminal specificity analyses and carry out (for example referring to Deacon people such as (Deacon), clinical endocrine metabolism magazine (J Clin Endocrinol Metab) (2000) 85:3575-3581).

Recently, shown that GIP promotes bone formation.Shown GIP activation osteoblast receptor, caused the increase of the synthetic and alkaline phosphatase activities of type i collagen albumen, the two is all relevant with bone formation.Shown that GIP suppresses osteoclast activity and differentiation in vitro.Shown that throwing the bone that can prevent to be caused by ovariectomy with GIP loses.Gip receptor (GIPR) rejects that mice shows that the bone size reduces, bone mass is lower, bone micro-structure and biochemical characteristic changes and the bone conversion parameter changes, particularly in bone formation.(for example referring to clock people such as (Zhong), U.S. physiology endocrine metabolism magazine (Am JPhysiol Endocrinol Metab) (2007) 292:E543-E548; Rich glug people such as (Bollag), endocrinology (Endocrinology) (2000) 141:1228-1235; Rich glug people such as (Bollag), molecular cell endocrinology (MolCell Endocrinol) (2001) 177:35-41; Thank to people such as (Xie), bone (Bone) (2005) 37:759-769; With build mountain people such as (Tsukiyama), molecular endocrinology (Mol Endocrinol) (2006) 20:1644-1651).

GIP be used to keep or the effectiveness of bone density improving or formation by United States Patent (USP) the 6th, the issue of 410, No. 508 (treat the bone mineralising with the GIP peptide and reduce) and obtain U.S.'s trade mark and Patent Office (United State Trademarkand Patent Office) approval by throwing.Yet all there is the shortage of oral biological usability in present GIP peptide agonists, thereby the negative effect patient compliance.A kind of attractive alternative method is that a kind of Orally active compositions of exploitation is to increase the active endogenous degree of GIP.

C.GPR119

GPR119 is a kind of G protein-coupled receptor (GPR119; For example, human GPR119,

Deposit numbering AAP72125 and its allele; For example, mice GPR119,

Deposit numbering AY288423 and its allele).Activate the rising that causes cAMP content in the cell as the GPR119 that is caused by agonist, this is with consistent with the GPR119 of Gs coupling.In patent documentation, GPR119 is called as RUP3 (for example, the international application case is PCT/US99/23687 number); GPR119 is also referred to as glucose dependency pancreotropic hormone receptor (GDIR).

D. DPP IV (DPP-IV)

DPP IV (DPP-IV, EC 3.4.14.5) shows catalytic activity to multiple peptide substrates, and described substrate comprises peptide hormone, neuropeptide and chemotactic factor.Incretin-glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic polypeptide (GIP) (homoiostasis that it stimulates glucose dependency insulin secretion and otherwise promotes blood glucose) are easy at 2 alanine places to cause its bioactive inactivation by the rapid cracking of DPP-IV.All with in vivo incretin effect enhancing is relevant with hereditism's weakening for the active pharmacology of DPP-IV.Second filial generation DPP-IV inhibitor LAF237 (vildagliptin (vildagliptin)) (Allan people such as (Ahren), clinical endocrine metabolism magazine (J ClinEndocrinol Metab) (2004) 89:2078-2084; With the great that of dimension people such as (Villhauer), pharmaceutical chemistry magazine (J MedChem) (2003) 46:2774-2789; The full text of its disclosure separately all is incorporated herein by reference) the present phase that is carrying out for type 2 diabetes mellitus, and other DPP-IV inhibitor is just carrying out clinical development, and it comprises MK-0431 (sitagliptin (sitagliptin)), BMS-477118 (Sa Kelieting (saxagliptin)), PSN-9301, T-6666, PHX-1149 and SYR-322 (A Gelieting (alogliptin)).Sitagliptin (Januvia ^TMSitagliptin phosphate) food and drug administration (U.S.Food and Drug Adiministration) approval is used to improve type 2 diabetes mellitus patient's blood sugar content recently.

Because the incretin hormone is not unique substrate of DPP-IV, therefore worry may produce unwanted side effect (for example referring to old people such as (Chen) to the cracked inhibitory action of other endogenous DPP-IV substrate, biological regulation and control stable pharmaceutical magazine (J Biol Regul Homeost Agents) (2004) 18:47-54, being incorporated herein by reference in full of its disclosure).Therefore, identify and a kind ofly can not rely on that to use DPP-IV inhibitor or the mode by using in fact the endogenous GIP live vol that obtains to increase than present DPP-IV inhibitor of expecting the concentration that concentration is low will be favourable.

Summary of the invention

The accident that the present invention relates to the applicant is found, promptly throws with GPR119 agonist (for example by oral) and can act on the GPR119 receptor to increase individual GIP content.The applicant shows that further the combination of GPR119 agonist and DPP IV (DPP-IV) inhibitor can provide the effect that the individual GIP content of increase that is provided by the DPP-IV inhibitor only is provided.The present invention relates to the GPR119 agonist, and the combination of a certain amount of GPR119 agonist and a certain amount of DPP-IV inhibitor, effect by the GPR119 agonist of described amount or the individual GIP content of increase that only provided by the DPP-IV inhibitor of described amount only is provided described combination provide to be higher than.The invention still further relates to the purposes of the combination of the purposes of GPR119 agonist and GPR119 agonist and DPP-IV inhibitor, it is used for the treatment of or prevents to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and be used to increase individual bone mass.Can be used for promoting (for example increasing) individual bone formation separately or with the GPR119 agonist of DPP-IV inhibitor combination.In certain embodiments, described individuality is human.

In first aspect, the invention provides the method that a kind of treatment or prevention are characterised in that the condition of illness of low bone mass, it comprises to the compositions that comprise GPR119 agonist of the individuality throwing that needs are arranged with the treatment effective dose.The method that the present invention provides a kind of treatment or prevention to be characterised in that the condition of illness of low bone mass in addition, it comprises to the individuality that needs are arranged throws and the medical composition that comprises GPR119 agonist and pharmaceutically acceptable supporting agent for the treatment of effective dose.In certain embodiments, the condition of illness that is characterised in that low bone mass is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man sick (Paget ' s disease), the bone forfeiture, osteolytic lesion, rachiocamposis and the height that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, be characterised in that the condition of illness that hangs down bone mass is osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.

The invention provides a kind of method that increases bone mass, it comprises to the individuality that needs are arranged throws and the compositions that comprises the GPR119 agonist for the treatment of effective dose.The present invention provides a kind of method that increases bone mass in addition, and it comprises to the individuality that needs are arranged throws the medical composition that comprises GPR119 agonist and pharmaceutically acceptable supporting agent with the treatment effective dose.In certain embodiments, the bmd (BMD) that need to increase the individuality of bone mass be lower than Young Adults with reference to the amount of meansigma methods greater than 1 (T-scoring＜-1) or more than or equal to 1.5 (T-scoring≤-1.5), the individual standard deviation in 2 (T-scoring≤-2) or 2.5 (T-scoring≤-2.5).In certain embodiments, need to increase the individual need treatment fracture of bone mass.In certain embodiments, individuality have traumatic fracture, for a long time the fracture or osteoporotic fracture.In certain embodiments, need to increase the individual need treatment osteopathia of bone mass.In certain embodiments, described osteopathia is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, osteopathia is an osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.In certain embodiments, the synosteosis that needs enhancing knitting, enhancing property long bone extension, strengthening property restoration inside growth or the increase of individual need after face reconstruction, upper jaw bone reconstruction, mandibular bone reconstruction, periodontal disease or exodontia of increase bone mass.

In certain embodiments, the GPR119 agonist is a selectivity GPR119 agonist.In certain embodiments, the GPR119 agonist is selected from the left hurdle of table D.

In certain embodiments, dispensing is oral.

In certain embodiments, the GPR119 agonist be with the amount that is enough to increase individual GIP content throw with.In certain embodiments, GIP content is the total GIP content of blood or blood plasma.In certain embodiments, GIP content is blood or blood plasma biological activity GIP content.

In certain embodiments, individuality is a vertebrates.In certain embodiments, individuality is a mammal.In certain embodiments, individuality is human.

In certain embodiments, dispensing is to carry out with single dose.

In certain embodiments, individuality is not human and offers medicine to be to carry out with single dose.

In certain embodiments, dispensing be greater than 24 days, greater than 36 days, greater than 48 days or greater than 60 days period in carry out with a plurality of dosage.In certain embodiments, a plurality of dosage are seriality dosage every day.In certain embodiments, individuality be not human and dispensing be greater than 24 days, greater than 36 days, greater than 48 days or greater than 60 days period in carry out with a plurality of dosage.In certain embodiments, individuality is not that the mankind and a plurality of dosage are seriality dosage every day.

In certain embodiments, individuality is human and offers medicine to be to carry out with single dose.

In certain embodiments, individuality is human and dispensing is to carry out with seriality dosage every day in the period of at least 2 days, at least 7 days, at least 14 days, at least 30 days or at least 60 days.

In certain embodiments, individuality is human and dispensing is greater than 8 weeks, greater than 12 weeks, greater than 16 weeks, greater than 20 weeks, greater than 24 weeks, greater than 28 weeks, carry out with a plurality of dosage greater than 32 weeks or in greater than the period in 36 weeks.In certain embodiments, a plurality of dosage are seriality dosage every day.

In second aspect, the invention provides the GPR119 agonist and treat the purposes that human body or animal body are characterised in that the condition of illness of low bone mass by therapy.In certain embodiments, human body or animal body are human bodies.In certain embodiments, the condition of illness that is characterised in that low bone mass is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, be characterised in that the condition of illness that hangs down bone mass is osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.

The invention provides the GPR119 agonist increases the purposes of the bone mass of human body or animal body by therapy.In certain embodiments, human body or animal body are human bodies.In certain embodiments, the bmd of human body or animal body (BMD) be lower than Young Adults with reference to the amount of meansigma methods greater than 1 (T-scoring＜-1) or more than or equal to 1.5 (T-scoring≤-1.5), the individual standard deviation in 2 (T-scoring≤-2) or 2.5 (T-scoring≤-2.5).In certain embodiments, human body or animal body need be treated fracture.In certain embodiments, human body or animal body have traumatic fracture, for a long time the fracture or osteoporotic fracture.In certain embodiments, human body or animal body need be treated osteopathia.In certain embodiments, osteopathia is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, osteopathia is an osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.In certain embodiments, human body or animal body need be rebuild at face, enhancing knitting, enhancing property long bone after upper jaw bone reconstruction, mandibular bone reconstruction, periodontal disease or the exodontia extend, enhancing property restoration inwardly growth or the synosteosis that increases.

In certain embodiments, the GPR119 agonist is that amount with the GIP content that is enough to increase human body or animal body provides.In certain embodiments, GIP content is the total GIP content of blood or blood plasma.In certain embodiments, GIP content is blood or blood plasma biological activity GIP content.

In certain embodiments, human body or animal body are human bodies.

In the third aspect, the invention provides the purposes of GPR119 agonist, it is used to make treatment or the individual medicine that is characterised in that the condition of illness of low bone mass of prevention.In certain embodiments, the condition of illness that is characterised in that low bone mass is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, be characterised in that the condition of illness that hangs down bone mass is osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.

The invention provides the purposes of GPR119 agonist, it is used to make the medicine that increases individual bone mass.In certain embodiments, Ge Ti bmd (BMD) be lower than Young Adults with reference to the amount of meansigma methods greater than 1 (T-scoring＜-1) or more than or equal to 1.5 (T-scoring≤-1.5), the individual standard deviation in 2 (T-scoring≤-2) or 2.5 (T-scoring≤-2.5).In certain embodiments, individual need treatment fracture.In certain embodiments, individuality have traumatic fracture, for a long time the fracture or osteoporotic fracture.In certain embodiments, individual need treatment osteopathia.In certain embodiments, osteopathia is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, osteopathia is an osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.In certain embodiments, the synosteosis of enhancing knitting, enhancing property long bone extension, strengthening property restoration inside growth or the increase of individual need after face reconstruction, upper jaw bone reconstruction, mandibular bone reconstruction, periodontal disease or exodontia.

In certain embodiments, the GPR119 agonist is to provide with the amount that is enough to increase individual GIP content.In certain embodiments, GIP content is the total GIP content of blood or blood plasma.In certain embodiments, GIP content is blood or blood plasma biological activity GIP content.

In fourth aspect, the invention provides the method that a kind of treatment or prevention are characterised in that the condition of illness of low bone mass, it comprises to the compositions that comprise GPR119 agonist and DPP-IV inhibitor of the individuality throwing that needs are arranged with the treatment effective dose.The method that the present invention provides a kind of treatment or prevention to be characterised in that the condition of illness of low bone mass in addition, it comprises to the individuality that needs are arranged throws and the medical composition that comprises GPR119 agonist and DPP-IV inhibitor and pharmaceutically acceptable supporting agent for the treatment of effective dose.In certain embodiments, the condition of illness that is characterised in that low bone mass is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, be characterised in that the condition of illness that hangs down bone mass is osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.

The invention provides a kind of method that increases bone mass, it comprises to the individuality that needs are arranged throws and the compositions that comprises GPR119 agonist and DPP-IV inhibitor for the treatment of effective dose.The present invention provides a kind of method that increases bone mass in addition, and it comprises to the individuality that needs are arranged throws the medical composition that comprises GPR119 agonist and DPP-IV inhibitor and pharmaceutically acceptable supporting agent with the treatment effective dose.In certain embodiments, the bmd (BMD) that need to increase the individuality of bone mass be lower than Young Adults with reference to the amount of meansigma methods greater than 1 (T-scoring＜-1) or more than or equal to 1.5 (T-scoring≤-1.5), the individual standard deviation in 2 (T-scoring≤-2) or 2.5 (T-scoring≤-2.5).In certain embodiments, need to increase the individual need treatment fracture of bone mass.In certain embodiments, individuality have traumatic fracture, for a long time the fracture or osteoporotic fracture.In certain embodiments, need to increase the individual need treatment osteopathia of bone mass.In certain embodiments, osteopathia is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, osteopathia is an osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.In certain embodiments, the synosteosis that needs enhancing knitting, enhancing property long bone extension, strengthening property restoration inside growth or the increase of individual need after face reconstruction, upper jaw bone reconstruction, mandibular bone reconstruction, periodontal disease or exodontia of increase bone mass.

In certain embodiments, the DPP-IV inhibitor is a selective DPP-IV inhibitors.In certain embodiments, the DPP-IV inhibitor is selected from the right hurdle of table D.

In certain embodiments, the GPR119 agonist is selected from the left hurdle of table D and the right hurdle that the DPP-IV inhibitor is selected from table D.

In certain embodiments, dispensing is oral.

In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be with the amount that is enough to increase individual GIP content throw with.In certain embodiments, GIP content is the total GIP content of blood or blood plasma.In certain embodiments, GIP content is blood or blood plasma biological activity GIP content.

In certain embodiments, dispensing is to carry out with single dose.

In certain embodiments, individuality is human and dispensing is greater than 8 weeks, greater than 12 weeks, greater than 16 weeks, greater than 20 weeks, greater than 24 weeks, greater than 28 weeks, carry out with a plurality of dosage greater than 32 weeks or in greater than the period in 36 weeks.

In aspect the 5th, the invention provides the purposes of the combination of GPR119 agonist and DPP-IV inhibitor, it is to treat the condition of illness that human body or animal body are characterised in that low bone mass by therapy.In certain embodiments, human body or animal body are human bodies.In certain embodiments, the condition of illness that is characterised in that low bone mass is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, be characterised in that the condition of illness that hangs down bone mass is osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.

The invention provides the purposes of the combination of GPR119 agonist and DPP-IV inhibitor, it is the bone mass that increases human body or animal body by therapy.In certain embodiments, human body or animal body are human bodies.In certain embodiments, the bmd of human body or animal body (BMD) be lower than Young Adults with reference to the amount of meansigma methods greater than 1 (T-scoring＜-1) or more than or equal to 1.5 (T-scoring≤-1.5), the individual standard deviation in 2 (T-scoring≤-2) or 2.5 (T-scoring≤-2.5).In certain embodiments, human body or animal body need be treated fracture.In certain embodiments, human body or animal body have traumatic fracture, for a long time the fracture or osteoporotic fracture.In certain embodiments, human body or animal body need be treated osteopathia.In certain embodiments, osteopathia is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, osteopathia is an osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.In certain embodiments, human body or animal body need be rebuild at face, enhancing knitting, enhancing property long bone after upper jaw bone reconstruction, mandibular bone reconstruction, periodontal disease or the exodontia extend, enhancing property restoration inwardly growth or the synosteosis that increases.

In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor is that amount with the GIP content that is enough to increase human body or animal body provides.In certain embodiments, GIP content is the total GIP content of blood or blood plasma.In certain embodiments, GIP content is blood or blood plasma biological activity GIP content.

In certain embodiments, human body or animal body are human bodies.

In aspect the 6th, the invention provides the purposes of the combination of GPR119 agonist and DPP-IV inhibitor, it is used to make treatment or the individual medicine that is characterised in that the condition of illness of low bone mass of prevention.In certain embodiments, the condition of illness that is characterised in that low bone mass is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, be characterised in that the condition of illness that hangs down bone mass is osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.

The invention provides the purposes of the combination of GPR119 agonist and DPP-IV inhibitor, it is used to make the medicine that increases individual bone mass.In certain embodiments, Ge Ti bmd (BMD) be lower than Young Adults with reference to the amount of meansigma methods greater than 1 (T-scoring＜-1) or more than or equal to 1.5 (T-scoring≤-1.5), the individual standard deviation in 2 (T-scoring≤-2) or 2.5 (T-scoring≤-2.5).In certain embodiments, individual need treatment fracture.In certain embodiments, individuality have traumatic fracture, for a long time the fracture or osteoporotic fracture.In certain embodiments, individual need treatment osteopathia.In certain embodiments, osteopathia is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.In certain embodiments, osteopathia is an osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.In certain embodiments, the synosteosis of enhancing knitting, enhancing property long bone extension, strengthening property restoration inside growth or the increase of individual need after face reconstruction, upper jaw bone reconstruction, mandibular bone reconstruction, periodontal disease or exodontia.

In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor is to provide with the amount that is enough to increase individual GIP content.In certain embodiments, GIP content is the total GIP content of blood or blood plasma.In certain embodiments, GIP content is blood or blood plasma biological activity GIP content.

In aspect the 7th, the invention provides a kind of method according to first aspect or fourth aspect, it further comprises according to circumstances differentiates individuality for be judged as described treatment of needs or prevention by the nursing staff and is characterised in that the condition of illness of low bone mass or described increase bone mass or can be by the step of the individuality of its benefit, and further comprises the step of realization of the therapeutic efficiency of the described throwing of discriminating and described compositions or described medical composition according to circumstances.

In certain embodiments, the invention provides a kind of method of first aspect, it further comprises differentiates individuality for be judged as described treatment of needs or prevention by the nursing staff and is characterised in that the condition of illness that hangs down bone mass or described increase bone mass or can be by the step of the individuality of its benefit.

In certain embodiments, the invention provides a kind of method of fourth aspect, it further comprises differentiates individuality for be judged as described treatment of needs or prevention by the nursing staff and is characterised in that the condition of illness that hangs down bone mass or described increase bone mass or can be by the step of the individuality of its benefit.

In certain embodiments, the invention provides a kind of method of first aspect, it further comprises the step of the realization of the therapeutic efficiency of differentiating described throwing and described compositions or described medical composition.

In certain embodiments, the invention provides a kind of method of fourth aspect, it further comprises the step of the realization of the therapeutic efficiency of differentiating described throwing and described compositions or described medical composition.

In certain embodiments, the invention provides a kind of method of first aspect, it further comprises differentiates individuality for be judged as described treatment of needs or prevention by the nursing staff and is characterised in that the condition of illness of low bone mass or described increase bone mass or can be by the step of the individuality of its benefit, and it further comprises the step of realization of the therapeutic efficiency of the described throwing of discriminating and described compositions or described medical composition.

In certain embodiments, the invention provides a kind of method of fourth aspect, it further comprises differentiates individuality for be judged as described treatment of needs or prevention by the nursing staff and is characterised in that the condition of illness of low bone mass or described increase bone mass or can be by the step of the individuality of its benefit, and it further comprises the step of realization of the therapeutic efficiency of the described throwing of discriminating and described compositions or described medical composition.

At individuality is that the nursing staff is doctor, nurse or nurse practitioner among some embodiment of the mankind.At individuality is among some embodiment of non-human Spine animal, and in the specific embodiment of non-human mammal, the nursing staff is the veterinary.

In certain embodiments, the realization of the therapeutic efficiency of the described dispensing of described discriminating comprises the bone mass content of measuring individuality.In certain embodiments, described measurement bone mass content comprises and uses dual-energy x-ray absorption process (DXA) to measure bone mass content.In certain embodiments, the described measurement of using DXA to measure bone mass content comprises use DXA measurement T-scoring.In certain embodiments, the described measurement of using DXA to measure the T-scoring comprises the T-scoring of using DXA to measure buttocks.Expect that clearly described measurement to bone mass content can comprise the technology (for example single X ray absorption process (SXA)) of use except that DXA and measure bone mass content [for example referring to World Health Organization's technical report book series 921 (World Health Organization Technical Report Series 921) (2003), osteoporosis prevention and processing (Prevention and Management of Osteoporosis)].

In certain embodiments, the realization of the therapeutic efficiency of the described dispensing of described discriminating comprises the GIP content of measuring individuality.In certain embodiments, GIP content is the total GIP content of blood or blood plasma.In certain embodiments, GIP content is blood or blood plasma biological activity GIP content.

Description of drawings

The present invention is graphic being illustrated of enclosing in conjunction with it, wherein:

Fig. 1 shows throwing and the pharmacodynamic analysis of GPR119 agonist to the influence of the blood GIP content of wild-type mice.A. the time-history analysis of using chemical compound 1Z to be carried out as the GPR119 agonist.B. the time-history analysis of using chemical compound 3Z to be carried out as the GPR119 agonist.C. the dose titration analysis of using chemical compound 3Z to be carried out as the GPR119 agonist.

Fig. 2 shows that throwing and GPR119 agonist are to the influence of GPR119 deletion form (rejecting) mice compared to the blood GIP content of wild-type mice.A. the comparison of using chemical compound 1Z to be carried out as the GPR119 agonist.B. the comparison of using chemical compound 2Z to be carried out as the GPR119 agonist.

Fig. 3 show throw with the combination of DPP-IV inhibitor and GPR119 agonist compared to the influence of independent throwing and DPP-IV inhibitor to the blood GIP content of wild-type mice.Use chemical compound 1Z as the GPR119 agonist.Use AR247810 as the DPP-IV inhibitor.

The specific embodiment

The present invention relates to some chemical compound or its pharmaceutically acceptable salt, it is used for the treatment of or prevents individuality to be characterised in that the condition of illness that hangs down bone mass, for example osteoporosis.The invention still further relates to some chemical compound or its pharmaceutically acceptable salt, it is used to increase individual bone mass.The applicant finds: throwing with GPR119 agonist (for example by oral) to individuality to increase individual GIP content.The GPR119 agonist can be used for treating or preventing to be characterised in that the condition of illness (for example osteoporosis) of low bone mass, and can be used for increasing individual bone mass.

The present invention relates to the combination of some chemical compound or its pharmaceutically acceptable salt, it is used for the treatment of or prevents individuality to be characterised in that the condition of illness that hangs down bone mass, for example osteoporosis.The invention still further relates to the combination of some chemical compound or its pharmaceutically acceptable salt, it is used to increase individual bone mass.The effect that only is higher than by the GPR119 agonist of described amount or the individual GIP content of increase that only provided by the DPP-IV inhibitor of described amount can be provided in the combination of a certain amount of GPR119 agonist and a certain amount of DPP-IV inhibitor.The combination of GPR119 agonist and DPP-IV inhibitor can be used for treating or prevents individuality to be characterised in that the condition of illness that hangs down bone mass, for example osteoporosis.The combination of GPR119 agonist and DPP-IV inhibitor can be used for increasing individual bone mass.

By using combination according to GPR119 agonist of the present invention and DPP-IV inhibitor, might more effectively treat or prevent to be characterised in that the condition of illness of low bone mass when using the GPR119 agonist more separately or using the DPP-IV inhibitor separately, thereby reduce the probability that produces the harmful side effect relevant with the active inhibition of DPP-IV.By using combination according to GPR119 agonist of the present invention and DPP-IV inhibitor, might more effectively increase bone mass when using the GPR119 agonist more separately or using the DPP-IV inhibitor separately, thereby reduce the probability that produces the harmful side effect relevant with the active inhibition of DPP-IV.The invention provides the method that novel, unexpected and favourable treatment or prevention are characterised in that the condition of illness (for example osteoporosis) of low bone mass and increase individual bone mass.The present invention provides the method for the individual GIP content of novel, unexpected and favourable increase in addition.

As used herein, the bonded molecule of polypeptid specificity (for example test compounds) with for example GPR119 or DPP-IV will be represented in term " part ".Part can be (for example) polypeptide, lipid, micromolecule, antibody.Chemical compound 1Z is the exemplary part (referring to table E, it lists chemical constitution and the chemical name of chemical compound 1Z) of GPR119 receptor polypeptides.The chemical compound that is disclosed in chemical compound 1Z and the international application PCT/US2004/001267 number (open with WO 2004/065380) is identical.(2-fluoro-4-methane sulfonyl-phenyl)-6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidines-1-yl]-5-nitro-pyrimidine-4-yl }-amine (referring to table E) is the exemplary part of GPR119 receptor polypeptides.Chemical compound 2Z is the exemplary part of GPR119 receptor polypeptides.The chemical compound that is disclosed in chemical compound 2Z and the international application PCT/US2004/022417 number (open with WO 2005/007658) is identical.Chemical compound 3Z is the exemplary part of GPR119 receptor polypeptides.The chemical compound that is disclosed in chemical compound 3Z and the international application PCT/US2004/022327 number (open with WO2005/007647) is identical.Endogenic ligand is the part as the endogenous native ligand of natural polypeptides (for example GPR119 or DPP-IV).Part may be " antagonist ", " agonist ", " partial agonist " or " inverse agonist " or the like.Part also may be " inhibitor ".

Table E

As used herein, term " agonist " will be represented by activating GPCR in conjunction with GPCR to cause the reagent (for example part) by the cell internal reaction of GPCR mediation.

As used herein, term " partial agonist " will be represented by activating GPCR in conjunction with GPCR causing the cell internal reaction by GPCR mediation, but its degree or grade are lower than the reagent (for example part) of full agonist.

Term " antagonist " will be illustrated in the roughly the same site of agonist or partial agonist on combine (and in specific embodiment competition in conjunction with) GPCR, but do not activate by the GPCR of activity form initial cell internal reaction, thereby and can suppress the reagent (for example part) of agonist or the caused cell internal reaction of partial agonist.Antagonist can't reduce the baseline cell internal reaction under the situation that does not have agonist or partial agonist usually.

Term " inverse agonist " will represent in conjunction with GPCR and will by the receptor of activity form initial baseline cell internal reaction be suppressed to and be lower than the active reagent of viewed normal benchmark (for example part) under the situation that does not have agonist or partial agonist.

As used herein, term " GPR119 agonist " is meant in conjunction with the GPR119 receptor and serves as the chemical compound of agonist.Chemical compound 1Z is exemplary GPR119 agonist (referring to table E, it lists chemical constitution and the chemical name of chemical compound 1Z).The chemical compound that is disclosed in chemical compound 1Z and the international application PCT/US2004/001267 number (open with WO2004/065380) is identical.(2-fluoro-4-methane sulfonyl-phenyl)-6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidines-1-yl]-5-nitro-pyrimidine-4-yl }-amine is exemplary GPR119 agonist.Chemical compound 2Z is exemplary GPR119 agonist.The chemical compound that is disclosed in chemical compound 2Z and the international application PCT/US2004/022417 number (open with WO2005/007658) is identical.Chemical compound 3Z is exemplary GPR119 agonist.The chemical compound that is disclosed in chemical compound 3Z and the international application PCT/US2004/022327 number (open with WO 2005/007647) is identical.

As used herein, term " selectivity GPR119 agonist " is meant for the GPR119 receptor and has the optionally GPR119 agonist that is better than one or more associated receptors (for example corticotropin releasing factor (CRF)-1 (CRF-1) receptor).Chemical compound 1Z is exemplary selectivity GPR119 agonist (referring to table E, it lists chemical constitution and the chemical name of chemical compound 1Z).The chemical compound that is disclosed in chemical compound 1Z and the international application PCT/US2004/001267 number (open with WO2004/065380) is identical.(2-fluoro-4-methane sulfonyl-phenyl)-6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidines-1-yl]-5-nitro-pyrimidine-4-yl }-amine is exemplary selectivity GPR119 agonist.Chemical compound 2Z is exemplary selectivity GPR119 agonist.The chemical compound that is disclosed in chemical compound 2Z and the international application PCT/US2004/022417 number (open with WO 2005/007658) is identical.Chemical compound 3Z is exemplary selectivity GPR119 agonist.The chemical compound that is disclosed in chemical compound 3Z and the international application PCT/US2004/022327 number (open with WO 2005/007647) is identical.

As used herein, term " DPP-IV inhibitor " is meant in conjunction with DPP-IV and suppresses the active chemical compound of DPP-IV dipeptidyl peptidase.AR247810 is exemplary DPP-IV inhibitor.

As used herein, term " selective DPP-IV inhibitors " is meant for DPP-IV and has the optionally DPP-IV inhibitor that is better than relevant peptidase (for example one or more in back proline lyases (PPCE), dipeptidyl peptidase II (DPP-II), dipeptidyl peptidase 8 (DPP-8) and the dipeptidyl peptidase 9 (DPP-9)).AR247810 is exemplary selective DPP-IV inhibitors.

Blood GIP concentration will be represented in term " blood GIP content ".In certain embodiments, blood GIP content is the total GIP content of blood.In certain embodiments, blood GIP content is blood biologic activity (biological activity) GIP content.In certain embodiments, biological activity GIP is the GIP that GIPR is had agonist activity.In certain embodiments, blood GIP content is blood plasma GIP content.

As used herein, term " individuality " is meant vertebrates, and it includes, but is not limited to Fish (for example commercially available breed fish, house pet fish etc.), amphibian (for example Rana nigromaculata, Bufo siccus, house pet amphibian etc.), reptile class (for example Serpentis, Eremiatis argi, Chelomia mydas (Linnaeus)., house pet reptile class etc.), birds (for example chicken, turkey, house pet birds etc.) and mammal (for example mice, rat, hamster, rabbit, pig, Canis familiaris L., cat, horse, cattle, sheep, goat, non-human primate, non-human mammal, house pet non-human mammal, the mankind etc.).In certain embodiments, individuality is Fish.In certain embodiments, individuality is an amphibian.In certain embodiments, individuality is a reptile class.In certain embodiments, individuality is birds.In certain embodiments, individuality is a turkey.In in the past 25 years, for the commercial selection pressure demand that generation increases for the skeleton integrity that has than the turkey of pectoralis major quality.Yet the chest muscle quality of increase is not attended by the compensatory variation of skeleton as yet, and this makes the turkey industry experience the increase of shank problem.Reported the long bone fracture of the male turkey of young adult.(for example referring to Crespo people such as (Crespo), poultry science (Poult Sci) (2000) 79:602-608.) in certain embodiments, individuality is a mammal.In certain embodiments, individuality is mice, rat, hamster, rabbit, pig, Canis familiaris L., cat, horse, cattle, sheep, goat, non-human primate or the mankind (it can individually or with any combination be included in the embodiments of the invention).In certain embodiments, individuality is a horse.Race horse (its be participate in for example horse racing, gallop along on horseback and the active horse of other competitive events) is easy to fracture.In certain embodiments, individuality is Canis familiaris L. or cat.In certain embodiments, individuality is human companion animals (for example Canis familiaris L., cat etc.), domestic animal (for example cattle, sheep, goat, pig, chicken etc.), (for example moves animal (for example horse, Canis familiaris L. etc.), a beast of burden (for example donkey, camel etc.) or wild animal (exotic animal), be found in animal in the zoo etc.), it can individually or with any combination be included in the embodiments of the invention.In certain embodiments, individuality is the non-human mammal.In certain embodiments, individuality is non-human primate (for example Rhesus Macacus, a chimpanzee etc.).In certain embodiments, individuality is human.

Term " needs to prevent or treatment " to be meant that by the nursing staff (for example be doctor, nurse or nurse practitioner under the mankind's situation as used in this article; Under the vertebrate situation of non-human is the veterinary, and is the non-human mammal in specific embodiment) individual need the done treatment judgement that maybe will from treatment, benefit.

Term " treatment effective dose " or " treatment effective dose " are meant and cause in tissue, system, animal, individuality or the mankind by research worker, biology or the reactive compound of medical response or the amount of medical agent that veterinary, doctor or other clinician sought as used in this article, and described biology or medical response comprise following one or more:

(1) prevent disease; For example, suffer from disease, condition of illness or disease, but do not experience as yet or manifest the pathology of described disease or individual prevent disease, condition of illness or the disease of symptom tending to,

(2) suppress disease; For example, align experience manifest the pathology of disease, condition of illness or disease or the individuality of symptom suppress disease, condition of illness or disease (promptly containing further developing of pathology and/or symptom) and

(3) improve disease; For example, align experience or manifest the pathology of disease, condition of illness or disease or the individuality of symptom improves disease, condition of illness or disease (promptly reversing pathology and/or symptom).

Term " therapeutic efficiency " is meant and causes in tissue, system, animal, individuality or the mankind by research worker, biology or medical response that veterinary, doctor or other clinician sought as used in this article, and described biology or medical response comprise following one or more:

Term " amount that can effectively prevent " is meant the medication amount with the appearance risk of the biology of prevention or the prevention of reduction desire or medical events.Under many situations, the amount that can effectively prevent is identical with the treatment effective dose.

Term " compositions " comprises expression the material of at least a component.

Term " active component " will be illustrated in the diagnosis, healing, mitigation, treatment of disease or the prevention pharmacological activity or other direct acting any component will be provided.

Term " medical composition " comprises at least a composition of active components with expression, and described thus compositions is used in detects in the mammal and treat.

" pharmaceutically acceptable " expression supporting agent, mediator, diluent, excipient and/or salt should be compatible with other composition of composite, and can be unharmful to its receiver.

Medication preparation and the physical form of dividing timing to adopt, for example tablet, capsule or injection will be represented in term " dosage form ".

" bone " means the connective tissue of the densification that forms most of vertebrates skeleton major part, semi-rigid, porous, calcification, and it comprises fine and close organic substrate and inorganic mineral components.Bone is to constitute any in the totally different structure on numerous anatomy of vertebrates skeleton.

Term " bone mass " and " bmd (BMD) " are used interchangeably in this article.Human BMD is normally measured by standard shadowgraph technology (dual-energy x-ray absorption process (DXA)).In the numerous technology of research and development with assessment BMD, DXA develops the highest and in checking technology the most completely biologically technically.Use the DXA technology of suitably adapting software also to be used in and assess BMD in the zooscopy reliably.DXA is used for the natural history and the reaction of assessment to treating of Diagnosis of osteoporosis, prognosis (fracture prediction), monitoring disease.

Term " low bone mass " is meant any minimizing or the reduction of individual bmd (BMD) as used in this article, and it comprises (the World Health Organization as World Health Organization (WHO); WHO) defined osteoporosis and osteopenia in the motion.WHO has been BMD value and Young Adults with normal definitions with reference to the difference of meansigma methods at 1 standard deviation with interior (T-scoring 〉=-1).WHO has been defined as osteopenia amount that the BMD value is lower than the Young Adults meansigma methods greater than 1 standard deviation, but the amount that is lower than this value is less than 2.5 standard deviations (T-scoring＜-1 and 〉-2.5).WHO with osteoporosis qualitative be osteopenic than severe form, and it to be defined as the amount that the BMD value is lower than the Young Adults meansigma methods be 2.5 standard deviations or above (T-scoring≤-2.5).(for example referring to World Health Organization's technical report book series 921 (World Health Organization Technical Report Series 921) (2003), osteoporosis prevention and processing (Prevention and Management of Osteoporosis), the full text of its disclosure is incorporated herein by reference).More generally osteopenia is defined as T-scoring less than-1 and greater than-2, and osteoporosis is defined as the T-scoring is less than or equal to-2.In certain embodiments of the present invention, the T-scoring is to be measured at buttocks by DXA.

Term " osteoporosis " is defined as the BMD value to be lower than Young Adults is 2 standard deviations or above (T-scoring≤-2) with reference to the amount of meansigma methods or refers to (for example refer to doctor, nurse or nurse practitioner under the mankind's situation by medical personnel as used in this article; Under the vertebrate situation of non-human, refer to the veterinary) diagnosis done.

Osteoporosis can be divided into constitutional or Secondary cases.(for example referring to World Health Organization's technical report book series 921 (World Health Organization Technical Report Series 921) (2003), osteoporosis prevention and processing (Prevention and Management of Osteoporosis)).As used herein, primary osteoporosis and secondary osteoporosis contained in term " osteoporosis ".In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.

" primary osteoporosis " and climacteric (naturality, early onset or operation property), old and feeble or both are relevant as used in this article.Should be appreciated that: in the present invention, the primary osteoporosis relevant, can individually or with any combination include among the embodiment with old and feeble relevant primary osteoporosis and with climacteric and old and feeble all relevant primary osteoporosis with climacteric (naturality, early onset or operation property).

As used in this article " secondary osteoporosis " be meant with climacteric or old and feeble irrelevant and with medical science condition of illness or the osteoporosis relevant with the use of medicament or medicine.The risk of osteoporosis increases and many medical science condition of illness (include but not limited to the E﹠M disorder, and malignant disease) about and relevant with the use of some medicament and medicine, the example of well-known described medicament of those skilled in the art and medicine is (for example referring to World Health Organization's technical report book series 921 (World Health Organization Technical Report Series 921) (2003), osteoporosis prevention and processing (Prevention and Management of Osteoporosis); WILLIAMS-DARLING Ton endocrinology (WilliamsTextbook of Endocrinology), the 10th edition; The full text of its disclosure is incorporated herein by reference).Secondary osteoporosis also may be relevant with braking.Can (for example under the mankind's situation, refer to doctor, nurse or nurse practitioner by medical personnel for use that is secondary to medical science condition of illness, medicament or medicine or arresting Diagnosis of osteoporosis; Under the vertebrate situation of non-human, refer to the veterinary) carry out.

Term " fracture " means rupturing fully or not exclusively, break or the crack of bone.Clinical examination and radiology performance are depended in the diagnosis of fracture usually.In the present invention, the fracture include, but is not limited to traumatic fracture, for a long time the fracture and pathologisch Bruch.

" traumatic fracture " should refer to the immediacy fracture as used in this article, and it relates to the wound above threshold with the local violence degree that exceeds the skeleton natural elasticity.Damage and the time damage of extremely common skin when it may be attended by soft tissue.Traumatic fracture can be closure (adjacent soft tissue may sustain damage, but the soft tissue portion that covers is kept largely).Traumatic fracture can be open (the fracture end of skeleton obtains to discharge because of large-area soft tissue injury, and therefore the pathogen that comes from the outside can directly enter wound).

" long-term fracture " should refer to chronic fracture, fatigue fracture, pressure fracture or I type spontaneous fracture as used in this article.

" pathologisch Bruch " should refer to II type spontaneous fracture as used in this article.Pathologisch Bruch is spontaneously to produce, rather than is caused by suitable wound.Skeleton may before systemic disease (for example osteoporosis, osteodystrophy or handkerchief Zhe Shi osteitis deformans) or local osseous lesion (for example transfer, radio osteonecrosis (radioosteonecrosis) or bone tumor) destroy.Referring to Adler (Adler), Crouse-Peter (Claus-Peter), osteopathia (BONEDISEASES), the 114th page (German Springer Verlag (Springer-Verlag, Germany), 2000 years).

Fracture also includes, but is not limited to diagonal torsion fracture, transverse fracture, multidirectional fracture, compression fractures, fracture of rib, spreading property fracture and fracture of femoral neck (Adler (Adler), Crouse-Peter (Claus-Peter), osteopathia (BONE DISEASES), Germany's Springer Verlag (Springer-Verlag, Germany) (2000)).

As used herein, term " is characterised in that the condition of illness of low bone mass " and includes, but is not limited to osteopenia, osteoporosis, primary osteoporosis, secondary osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, rachiocamposis and height reduction.In certain embodiments, secondary osteoporosis is relevant with medical science condition of illness.In certain embodiments, secondary osteoporosis is relevant with the use of medicament or medicine.In certain embodiments, secondary osteoporosis is relevant with braking.The condition of illness that is characterised in that low bone mass includes, but is not limited to handkerchief wise man bone forfeiture sick, that cause because of metastatic cancer and osteolytic lesion (for example by osteolytic lesion that neoplastic disease, X-ray therapy or chemotherapy caused).Be characterised in that the condition of illness of low bone mass also includes, but is not limited to the long-term complications of osteoporosis, for example rachiocamposis, height reduce and the restoration operation.Should be appreciated that: in the present invention, be characterised in that the condition of illness of low bone mass can individually or with any combination be included among the embodiment.(for example referring to World Health Organization's technical report book series 921 (World Health Organization Technical ReportSeries 921) (2003), osteoporosis prevention and processing (Prevention and Management ofOsteoporosis); WILLIAMS-DARLING Ton endocrinology (Williams Textbook of Endocrinology), the 10th edition, Larsen people such as (Larsen) compiles, (2002), W.B. Saunders publishing company (W.B.Saunders Company); And endocrinology and metabolism (Endocrinology and Metabolism), the 4th edition, Fei Lige people such as (Felig) compiles, (2001), Mai Geluo-hill plot book company (McGraw-Hill Book Company); It is disclosure be incorporated herein by reference in full separately.)

As used herein, " osteopathia " is meant and unusual relevant disease or the condition of illness of bone.The osteopathia that can treat by increase bone mass or osteogenesis according to the present invention includes, but is not limited to osteopenia, osteoporosis, primary osteoporosis, secondary osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, rachiocamposis and height and reduces.In certain embodiments, secondary osteoporosis is relevant with medical science condition of illness.In certain embodiments, secondary osteoporosis is relevant with the use of medicament or medicine.In certain embodiments, secondary osteoporosis is relevant with braking.Can be according to the present invention also include, but is not limited to handkerchief wise man bone forfeiture sick and that cause because of metastatic cancer by increasing osteopathia that bone mass or osteogenesis treat.The destructive bone disorders that can treat by increase bone mass or osteogenesis according to the present invention includes, but is not limited to osteoporosis, osteoarthritis and osteolytic lesion (for example osteolytic lesion that is caused by neoplastic disease, X-ray therapy or chemotherapy).Should be appreciated that: in the present invention, the osteopathia that can treat by increase bone mass or osteogenesis according to the present invention can individually or with any combination be included among the embodiment.(for example referring to World Health Organization's technical report book series 921 (World HealthOrganization Technical Report Series 921) (2003), osteoporosis prevention and processing (Preventionand Management of Osteoporosis); WILLIAMS-DARLING Ton endocrinology (Williams Textbook ofEndocrinology), the 10th edition, Larsen people such as (Larsen) compiles, (2002), W.B. Saunders publishing company (W.B.Saunders Company); And endocrinology and metabolism (Endocrinology and Metabolism), the 4th edition, Fei Lige people such as (Felig) compiles, (2001), Mai Geluo-hill plot book company (McGraw-Hill Book Company); It is disclosure be incorporated herein by reference in full separately).

The present invention also relates to from other condition of illness that obtains benefit according to the present invention by the treatment of increase bone mass or osteogenesis the synosteosis that it includes, but is not limited to the enhancing knitting after face reconstruction, upper jaw bone reconstruction, mandibular bone reconstruction, periodontal disease or exodontia, the extension of enhancing property long bone, the inside growth of enhancing property restoration and increases.

Chemical group, part or group

Term " C _1-5Acyl group " C that is connected with carbonyl of expression _1-5Alkyl, wherein the definition of alkyl has and described identical definition herein; Some examples include, but is not limited to acetyl group, propiono, positive bytyry, isobutyryl, secondary bytyry, uncle's bytyry (being valeryl), valeryl or the like.

Term " C _1-5Acyloxy " acyl group that is connected with oxygen atom of expression, wherein acyl group has and described identical definition herein; Some examples include, but is not limited to acetoxyl group, propionyloxy, butyryl acyloxy, isobutyl acyloxy, secondary butyryl acyloxy, uncle's butyryl acyloxy or the like.

Term " C _1-6The acyl group sulfonamide " be meant and the direct-connected C of the nitrogen of sulfonamide _1-6Acyl group, wherein C _1-6The definition of acyl group and sulfonamide has and described identical implication herein, and C _1-6The acyl group sulfonamide can be expressed from the next:

Alkyl.

Some embodiments of the present invention be when the acyl group sulfonamide be C _1-5During the acyl group sulfonamide, some embodiment are C _1-4The acyl group sulfonamide, some embodiment are C _1-3The acyl group sulfonamide, and some embodiment are C _1-2The acyl group sulfonamide.The example of acyl group sulfonamide include, but is not limited to the acetyl group sulfamoyl [S (=O) ₂NHC (=O) Me], the propiono sulfamoyl [S (=O) ₂NHC (=O) Et], isobutyryl sulfamoyl, bytyry sulfamoyl, 2-methyl-bytyry sulfamoyl, 3-methyl-bytyry sulfamoyl, 2,2-dimethyl-propiono sulfamoyl, valeryl sulfamoyl, 2-methyl-valeryl sulfamoyl, 3-methyl-valeryl sulfamoyl, 4-methyl-valeryl sulfamoyl or the like.

Term " C _2-6Thiazolinyl " there is the group that contains 2 to 6 carbon of at least one carbon-carbon double bond in expression, and some embodiment are 2 to 4 carbon, and some embodiment are 2 to 3 carbon, and some embodiment have 2 carbon.E isomer and Z isomer contained in term " thiazolinyl ".In addition, term " thiazolinyl " comprises dialkylene and trialkenyl.Therefore, if there are two keys more than, so described key may all be the mixture of E isomer or Z isomer or E isomer and Z isomer.The example of thiazolinyl comprises vinyl, pi-allyl, crotyl, 3-cyclobutenyl, pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexyl, 2,4-hexadienyl or the like.

Term " C as used in this article _1-4Alkoxyl " expression and the direct-connected alkyl as defined herein of oxygen atom.Example comprises methoxyl group, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, tert-butoxy, isobutoxy, sec-butoxy or the like.

Term " C _1-8Alkyl " expression contains the straight or branched carbon back of 1 to 8 carbon, and some embodiment are 1 to 6 carbon, and some embodiment are 1 to 3 carbon, and some embodiment are 1 or 2 carbon.The example of alkyl include, but is not limited to methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, sec-butyl, isobutyl group, the tert-butyl group, amyl group, isopentyl, tertiary pentyl, neopentyl, 1-methyl butyl [promptly-CH (CH ₃) CH ₂CH ₂CH ₃], the 2-methyl butyl [promptly-CH ₂CH (CH ₃) CH ₂CH ₃], n-hexyl or the like.

Term " C _1-4The alkyl formamides base " or " C _1-4Alkyl formamides " the single C that is connected with the nitrogen of amide groups of expression _1-4Alkyl, wherein alkyl has and the identical definition of finding herein.C _1-5The alkyl formamides base can be expressed from the next:

Alkyl,

Alkyl.

Example includes, but is not limited to N-methylformamide, N-ethyl-formamide, N-n-pro-pyl Methanamide, N-isopropyl Methanamide, N-normal-butyl Methanamide, N-sec-butyl Methanamide, N-isobutyl group Methanamide, N-tert-butylformamide or the like.

Term " C _1-3Alkylidene " be meant C _1-3Bivalence straight chain carbon back.In certain embodiments, C _1-3Alkylidene is meant (for example)-CH ₂-,-CH ₂CH ₂-,-CH ₂CH ₂CH ₂-or the like.In certain embodiments, C _1-3Alkylidene is meant-CH-,-CHCH ₂-,-CHCH ₂CH ₂-or the like, wherein these examples are relevant with " A " usually.

Term " C _1-4Alkyl sulphinyl " expression and formula-S (O)-the C that is connected of sulfoxide group _1-4Alkyl, wherein said alkyl have and described identical definition herein.Example includes, but is not limited to methylsulfinyl, ethyl sulfinyl, n-pro-pyl sulfinyl, isopropyl sulfinyl, normal-butyl sulfinyl, sec-butyl sulfinyl, isobutyl group sulfinyl, tert-butyl group or the like.

Term " C _1-4Alkyl sulfonamide " be meant group

Alkyl,

Alkyl,

C wherein _1-4Alkyl has and described identical definition herein.

Term " C _1-4Alkyl sulphonyl " expression and formula-S (O) ₂-the C that connects of sulfuryl _1-4Alkyl, wherein said alkyl have and described identical definition herein.Example includes, but is not limited to methyl sulphonyl, ethylsulfonyl, n-pro-pyl sulfonyl, isopropyl sulfonyl, normal-butyl sulfonyl, sec-butyl sulfonyl, isobutyl group sulfonyl, tert-butyl group or the like.

Term " C _1-4The alkyl sulfenyl " C that is connected with the sulfenyl of formula-S-of expression _1-4Alkyl, wherein said alkyl have and described identical definition herein.It (is CH that example includes, but is not limited to the methyl sulfenyl ₃S-), ethyl sulfenyl, n-pro-pyl sulfenyl, isopropyl sulfenyl, normal-butyl sulfenyl, sec-butyl sulfenyl, isobutyl group sulfenyl, tert-butyl group or the like.

Term " C _1-4The alkylthio Methanamide " expression following formula thioamides:

Alkyl,

Alkyl,

C wherein _1-4Alkyl has and described identical definition herein.

Term " C _1-4The alkyl sulfide urea groups " group of expression-NC (S) N-, wherein a kind of situation is that two nitrogen are through identical or different C _1-4Alkyl replaces, and alkyl has and described identical definition herein.The example of alkyl sulfide urea groups includes, but is not limited to CH ₃NHC (S) NH-, NH ₂C (S) NCH ₃-, (CH ₃) ₂N (S) NH-, (CH ₃) ₂N (S) NH-, (CH ₃) ₂N (S) NCH ₃-, CH ₃CH ₂NHC (S) NH-, CH ₃CH ₂NHC (S) NCH ₃-or the like.

Term " C _1-4The alkyl urea groups " group of expression-NC (O) N-, wherein a kind of situation is that two nitrogen are through identical or different C _1-4Alkyl replaces, and wherein alkyl has and described identical definition herein.The example of alkyl urea groups includes, but is not limited to CH ₃NHC (O) NH-, NH ₂C (O) NCH ₃-, (CH ₃) ₂N (O) NH-, (CH ₃) ₂N (O) NH-, (CH ₃) ₂N (O) NCH ₃-, CH ₃CH ₂NHC (O) NH-, CH ₃CH ₂NHC (O) NCH ₃-or the like.

Term " C _2-6Alkynyl " represent to contain 2 to 6 carbon and the triple-linked group of at least one carbon carbon, some embodiment are 2 to 4 carbon, some embodiment are 2 to 3 carbon, and some embodiment have 2 carbon.The example of alkynyl includes, but is not limited to acetenyl, 1-propinyl, 2-propynyl, ethyl acetylene base, 2-butyne base, 3-butynyl, 1-pentynyl, valerylene base, 3-pentynyl, 4-pentynyl, 1-hexin base, 2-hexin base, 3-hexin base, 4-hexin base, 5-hexin base or the like.Term " alkynyl " comprises diine and three alkynes.

Term " amino " expression group-NH ₂

Term " C _1-4Alkyl amino " one of expression and the alkyl that is connected of amino, wherein said alkyl has and described identical implication herein.Some embodiment include, but is not limited to methylamino, ethylamino, n-pro-pyl amino, isopropyl amino, normal-butyl amino, sec-butyl amino, isobutylamino, tert-butyl group amino or the like.Some embodiment are " C _1-2Alkyl amino ".

Term " aryl " expression contains the aromatic series cyclic group of 6 to 10 ring carbon.Example comprises phenyl and naphthyl.

The C that term " aryl alkyl " definition further replaces through aryl ₁-C ₄Alkylidene (for example-CH ₂-,-CH ₂CH ₂-or the like).The example of " aryl alkyl " comprises benzyl, inferior phenethyl or the like.

The single aryl that term " aryl carboxamides base " expression is connected with the nitrogen of amide groups, wherein aryl has and the identical definition of finding herein.Example is the N-phenyl formamide.

Term " aryl-ureido " expression group-NC (O) N-, one of them nitrogen-atoms replaces through aryl.

Term " benzyl " expression group-CH ₂C ₆H ₅

Term " C _1-6Alkoxy carbonyl group " be meant the C of carboxylic acid _1-6Arrcostab, wherein said alkyl as defined herein.In certain embodiments, C _1-6Alkoxy carbonyl group is with the nitrogen-atoms bond and form carbamate groups (N-COO-C for example _1-6Alkyl).In certain embodiments, C _1-6Alkoxy carbonyl group be ester (for example-COO-C _1-6Alkyl).Example includes, but is not limited to methoxycarbonyl group, carbethoxyl group, the third oxygen carbonyl, the different third oxygen carbonyl, butoxy carbonyl, secondary butoxy carbonyl, isobutyl boc, tertbutyloxycarbonyl, positive penta oxygen carbonyl, isoamyl oxygen carbonyl, uncle's penta oxygen carbonyl, new penta oxygen carbonyl, just own oxygen carbonyl or the like.

Term " Methanamide " is meant group-CONH ₂

Term " carboxyl " expression group-CO ₂H; Be also referred to as hydroxy-acid group.

Term " cyano group " expression group-CN.

Term " C _3-7Cycloalkenyl group " expression contains the non-aromatic cyclic groups of 3 to 6 two keys of ring carbon and at least one; Some embodiment contain 3 to 5 carbon; Some embodiment contain 3 to 4 carbon.Example comprises cyclopropanyl, cyclobutane base, cyclopentenyl, cyclopentenyl, cyclohexenyl group or the like.

Term " C _3-7Cycloalkyl " expression contains the saturated cyclic group of 3 to 6 carbon; Some embodiment contain 3 to 5 carbon; Some embodiment contain 3 to 4 carbon.Example comprises cyclopropyl, cyclobutyl, cyclopenta, cyclopenta, cyclohexyl, suberyl or the like.

Term " C _4-8Diacylamino group " represent and the amino of two defined acyl group bonds that wherein said acyl group can be identical or different herein, for example:

C _4-8The example of diacylamino group includes, but is not limited to diacetyl amino, dipropyl acyl amino, acetyl group propiono amino or the like.

Term " C _2-6Dialkyl amido " represent that wherein alkyl has and described identical definition herein through the amino of two identical or different alkyl replacements.Some examples include, but is not limited to dimethylamino, Methylethyl amino, diethylamino, methyl-propyl amino, isopropyl methyl amino, ethyl propyl amino, ethyl isopropyl amino, dipropyl amino, propyl group isopropyl amino or the like.Some embodiment are " C _2-4Dialkyl amido ".

Term " C _1-4The dialkylformamide base " or " C _1-4Dialkylformamide " two identical or different alkyl of being connected with amide groups of expression, wherein alkyl has and described identical definition herein.C _1-4The dialkylformamide base can be represented by following groups:

C wherein _1-4Have and described identical definition herein.The example of dialkylformamide includes, but is not limited to N, dinethylformamide, N-methyl-N-ethyl-formamide, N, N-diethylformamide, N-methyl-N-isopropyl propyl group Methanamide or the like.

Term " C _2-6The dialkyl group sulfonamide " a kind of in the following groups shown in being meant hereinafter:

C wherein _1-3Have and described identical definition herein, for example (but being not limited to) methyl, ethyl, n-pro-pyl, isopropyl or the like.

Term " C _2-6Dialkyl group thioformamide base " or " C _2-6The dialkyl group thioformamide " two identical or different alkyl of being connected with the thioamides base of expression, wherein alkyl has and described identical definition herein.C _1-4Dialkyl group thioformamide base can be represented by following groups:

The example of dialkyl group thioformamide includes, but is not limited to N, N-dimethyl thioformamide, N-methyl-N-ethylenebis dithiocarbamate Methanamide or the like.

Term " C _2-6The dialkyl group sulfuryl amino " be meant and defined two C herein _1-3The amino of alkyl sulphonyl bond.

Term " ethynylene " is meant following represented carbon carbon triple bond group:

Term " formoxyl " is meant group-CHO.

Term " C _1-4The halogen alkoxyl " expression and the direct-connected alkylhalide group as defined herein of oxygen atom.Example includes, but is not limited to difluoro-methoxy, trifluoromethoxy, 2,2,2-trifluoro ethoxy, five fluorine ethyoxyls or the like.

Term " C _1-4Alkylhalide group " expression C as defined herein _1-4Alkyl, wherein said alkyl replaces up to being substituted fully through halogen, and the C that is substituted fully _1-4Alkylhalide group can be by formula C _nL _2n+1Expression, wherein L is that halogen and " n " they are 1,2,3 or 4; When having an above halogen, then it can be identical or different and is selected from the group that is made up of F, Cl, Br and I, is F in specific embodiment.C _1-4The example of alkylhalide group includes, but is not limited to methyl fluoride, difluoromethyl, trifluoromethyl, chlorodifluoramethyl-, 2,2,2-trifluoroethyl, pentafluoroethyl group or the like.

Term " C _1-4The alkylhalide group Methanamide " the defined herein alkyl formamides base of expression, wherein said alkyl replaces up to being substituted fully (by formula C through a halogen _nL _2n+1Expression, wherein L is that halogen and " n " they are 1,2,3 or 4).When having an above halogen, it can be identical or different and is selected from the group that is made up of F, Cl, Br and I, is F in specific embodiment.

Term " C _1-4The alkylhalide group sulfinyl " expression and formula-S (O)-the alkylhalide group that is connected of sulfoxide group, wherein said alkylhalide group has and described identical definition herein.Example includes, but is not limited to trifluoromethyl sulphinyl base, 2,2,2-trifluoroethyl sulfinyl, 2,2-two fluoro ethyl sulfinyls or the like.

Term " C _1-4The alkylhalide group sulfonyl " expression and formula-S (O) ₂-the alkylhalide group that connects of sulfuryl, wherein alkylhalide group has and described identical definition herein.Example includes, but is not limited to trifluoromethyl sulfonyl, 2,2,2-trifluoroethyl sulfonyl, 2,2-difluoro ethylsulfonyl or the like.

Term " C _1-4The alkylhalide group sulfenyl " expression and the direct-connected alkylhalide group of sulfur, wherein said alkylhalide group has and described identical implication herein.It (is CF that example includes, but is not limited to the trifluoromethyl sulfenyl ₃S-), 1,1-two fluoro ethyl sulfenyls, 2,2,2-trifluoroethyl sulfenyl or the like.

Term " halogen " or " halogen " expression fluorine, chlorine, bromine or iodine base.

Term " C _1-2Inferior assorted alkyl " be meant and be selected from O, S, S (O), S (O) ₂C with the hetero atom bond of NH _1-2Alkylidene.Some representative example include, but is not limited to the group of following formula:

Or the like.

Term " heteroaryl " expression can be the aromatic ring system of monocycle, two condensed ring or three condensed ring, and wherein the hetero atom of the group of at least one ring carbon through being selected from (but being not limited to) and being made up of O, S and N is replaced, and wherein said N can be according to circumstances through H, C _1-4Acyl group or C _1-4Alkyl replaces.The example of heteroaryl includes, but is not limited to pyridine radicals, benzofuranyl, pyrazinyl, pyridazinyl, pyrimidine radicals, triazine radical, quinoline, benzoxazole, benzothiazole, 1H-benzimidazole, isoquinolin, quinazoline, quinoxaline or the like.In certain embodiments, described heteroaryl atom is O, S, NH, and example includes, but is not limited to pyrroles, indole or the like.

Term " heterocyclic radical " expression non-aromatic carbocyclic ring (i.e. cycloalkyl as defined herein or cycloalkenyl group), one of them, the hetero atom of the group of two or three ring carbon through being selected from (but being not limited to) and being made up of O, S, N replaces, wherein said N can be according to circumstances through H, C _1-4Acyl group or C _1-4Alkyl replaces, and ring carbon atom replaces through oxo base or sulfur oxo base according to circumstances, thereby forms carbonyl or thiocarbonyl.Heterocyclic radical is the ring that contains 3,4,5,6 or 7 members.The example of heterocyclic radical includes, but is not limited to ethylene imine-1-base, ethylene imine-2-base, azetidine-1-base, azetidine-2-base, azetidine-3-base, piperidines-1-base, piperidin-4-yl, morpholine-4-base, piperazine-1-base, piperazine-4-base, pyrrolidine-1-base, pyrrolidine-3-base, [1,3]-dioxolanes-2-base or the like.

The heterocyclic radical as defined herein of the direct bond of carbon of term " heterocyclic radical-carbonyl " expression and carbonyl (being C=O).In certain embodiments, the ring nitrogen of described heterocyclic radical and carbonyl bond form amide.Example includes, but is not limited to

Or the like.

In certain embodiments, ring carbon and carbonyl bond form ketone group.Example includes, but is not limited to:

Or the like.

Term " heterocyclic radical-oxygen base " is meant the heterocyclic radical as defined herein with the direct bond of oxygen atom.Example comprises following groups:

Or the like.

Term " heterocyclic radical formamido " expression has the heterocyclic radical as defined herein of ring nitrogen, and the direct bond of wherein said ring nitrogen and carbonyl forms amide.Example includes, but is not limited to:

Or the like.

Term " heterocyclic radical sulfonyl " expression has the heterocyclic radical as defined herein of ring nitrogen, wherein said ring nitrogen and SO ₂The direct bond of group forms sulfonamide.Example includes, but is not limited to:

Or the like.

Term " hydroxyl " is meant group-OH.

Term " hydroxyl amino " is meant group-NHOH.

Term " nitro " is meant group-NO ₂

Term " C _4-7Oxo-cycloalkyl " be meant C as defined herein _4-7Cycloalkyl, one of them ring carbon is replaced through carbonyl.C _4-7The example of oxo-cycloalkyl includes, but is not limited to 2-oxo-cyclobutyl, 3-oxo-cyclobutyl, 3-oxo-cyclopenta, 4-oxo-cyclohexyl or the like, and is represented by following structure respectively:

Term " perfluoroalkyl " expression-C _nF _2n+1Group; In other words, perfluoroalkyl alkyl as defined herein that to be alkyl replace fully through fluorine atom and the subclass that therefore is regarded as alkylhalide group.The example of perfluoroalkyl comprises CF ₃, CF ₂CF ₃, CF ₂CF ₂CF ₃, CF (CF ₃) ₂, CF ₂CF ₂CF ₂CF ₃, CF ₂CF (CF ₃) ₂, CF (CF ₃) CF ₂CF ₃Or the like.

Term " phenoxy group " is meant group C ₆H ₅O-.

Term " phenyl " is meant group C ₆H ₅-.

Term " phosphonato " is meant the group with the following chemical structure:

Term " sulfonamide " is meant group-SO ₂NH ₂

Term " sulfonic acid " is meant group-SO ₃H.

Term " tetrazole radical " is meant the quinary heteroaryl of following formula:

In certain embodiments, described tetrazole radical on 1 or 5 respectively through being selected from by C _1-3Alkyl, C _1-3Alkylhalide group and C _1-3The group of the group that alkoxyl is formed further replaces.

Term " mercaptan " expression group-SH.

The material of natural generation that term " endogenous " will be represented will be individual (for example and be not limited to the mankind).In contrast, " non-endogenous " will represent not to be the material by individual (for example and be not limited to the mankind) natural generation.

The cell of carrier will be represented to include in term " host cell ".In this article, carrier will contain the nucleic acid of coding GPCR or gpcr fusion protein usually, and it operatively is connected with suitable promoter sequence to allow to take place the expression of GPCR or gpcr fusion protein.In specific embodiment, host cell is an eukaryotic host cell.In certain embodiments, eukaryotic host cell is a mammalian host cell.In certain embodiments, eukaryotic host cell is a yeast host cell.In certain embodiments, eukaryotic host cell is the melanocyte host cell.

Term " contact " flocks together at least two parts expression.

Term " regulation and control " or " modification " will be used in reference to the increase or the reduction of amount, quality or the effect of concrete activity, function or molecule.As an illustration and and unrestricted, the agonist of G protein-coupled receptor, partial agonist, inverse agonist and antagonist all are the regulators of described receptor.

Term " micromolecule " will be used to represent that molecular weight is less than about 10, the chemical compound of 000 gram/mole, it comprises peptide, peptide mimics, aminoacid, amino acid analogue, polynucleotide, polynucleotide analog, nucleotide, nucleotide analog, organic compound or inorganic compound (promptly comprise assorted organic compound or organo-metallic compound), with and salt, ester and other pharmaceutically acceptable form.In certain embodiments, micromolecule is the organic or inorganic chemical compound of molecular weight less than about 5,000 gram/moles.In certain embodiments, micromolecule is the organic or inorganic chemical compound of molecular weight less than about 1,000 gram/mole.In certain embodiments, micromolecule is the organic or inorganic chemical compound of molecular weight less than about 800 gram/moles.In certain embodiments, micromolecule is the organic or inorganic chemical compound of molecular weight less than about 600 gram/moles.In certain embodiments, micromolecule is the organic or inorganic chemical compound of molecular weight less than about 500 gram/moles.

Amino acid abbreviations used herein is listed among the table F:

Table F

Alanine	ALA	A
Alanine	ALA	A	Arginine	ARG	R
Agedoite	ASN	N	Arginine	ARG	R
Agedoite	ASN	N	Aspartic acid	ASP	D
Cysteine	CYS	C	Aspartic acid	ASP	D
Cysteine	CYS	C	Glutamic acid	GLU	E
Glutamine	GLN	Q	Glutamic acid	GLU	E
Glutamine	GLN	Q	Glycine	GLY	G
Histidine	HIS	H	Glycine	GLY	G
Histidine	HIS	H	Isoleucine	ILE	I
Leucine	LEU	L	Isoleucine	ILE	I
Leucine	LEU	L	Lysine	LYS	K
Methionine	MET	M	Lysine	LYS	K
Methionine	MET	M	Phenylalanine	PHE	F
Proline	PRO	P	Phenylalanine	PHE	F
Proline	PRO	P	Serine	SER	S
Threonine	THR	T	Serine	SER	S
Threonine	THR	T	Tryptophan	TRP	W
Tyrosine	TYR	Y	Tryptophan	TRP	W
Tyrosine	TYR	Y	Valine	VAL	V

Term " polypeptide " will refer to polymer of amino acid, and irrelevant with the length of polymer.Therefore, peptide, oligopeptide and protein all are included in the definition of polypeptide.This term is not also specified or is got rid of trim after the polypeptide expression.For instance, the term polypeptide is clearly contained the covalently bound polypeptide that comprises glycosyl, acetyl group, phosphate group, lipid groups or the like.

Monoclonal antibody and polyclonal antibody planned to contain in this article in term " antibody ".

Term " second message,second messenger " will be represented the factor receptor activation and the cell internal reaction of generation.The second message,second messenger can comprise (for example) 1,4,5-InsP3 (IP ₃), DG (DAG), ring-type AMP (cAMP), ring-type GMP (cGMP), map kinase activity, MAPK/ERK kinase kinase-1 (MEKK1) activity and Ca ²⁺Second message,second messenger's reaction can be through measuring to measure receptor activation.

Term " function of receptors " will refer to that receptor acceptance stimulates and regulate the normal running of the effect in the cell, it includes, but is not limited to regulator gene and transcribes, regulates ionic inflow or outflow, realization catalytic reaction and/or pass through G protein regulation activity, for example causes that the second message,second messenger reacts.

The term " stimulation " relevant with term " reaction " or " function of receptors " will be represented to compare with the situation that does not have chemical compound, exist under the situation of chemical compound reaction or function of receptors to obtain increasing.

The term " inhibition " relevant with term " reaction " or " function of receptors " will be represented to compare with the situation that does not have chemical compound, exist under the situation of chemical compound reaction or function of receptors to be reduced or prevent.

When numerical range is provided, offer some clarification in addition unless should be appreciated that context, otherwise any other the described or intermediate value in each intermediate value between the upper and lower bound of described scope (be accurate to lower limit 1/10th) and the described scope all is covered by among the present invention.During these upper and lower bounds more among a small circle can independently be included in more among a small circle, and also be covered by among the present invention, it is subordinated to the boundary that any given row in the described scope is removed.When described scope comprises one or two boundary, do not comprise that one or two scope in those included boundaries is also included among the present invention.

The GPR119 agonist

In certain embodiments, GPR119 is mammal GPR119.In certain embodiments, GPR119 is rodent or primate GPR119.In certain embodiments, GPR119 is human GPR119.

The kind (including but not limited to novel therapeutic combination of the present invention) that can be used for the GPR119 agonist in the compositions and methods of the invention comprises the GPR119 receptor is shown the chemical compound that can accept high-affinity.GPR119 agonist or pharmaceutically acceptable salt can be any agonist, and are selectivity GPR119 agonist in specific embodiment.

The case description of GPR119 agonist in international application case PCT/US2004/001267 number (open) with WO04/065380, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/US2004/001267 number is formula (I) chemical compound:

Wherein:

A and B are independently for according to circumstances through 1 to 4 methyl substituted C _1-3Alkylidene;

D is O, S, S (O), S (O) ₂, CR ₂R ₃Or N-R ₂

V is selected from by C _1-3Alkylidene, ethynylene and C _1-2The group that inferior assorted alkyl is formed, wherein each group replaces through 1 to 4 substituent group according to circumstances, and described substituent group is selected from by C _1-3Alkyl, C _1-4Alkoxyl, carboxyl, cyano group, C _1-3The group that alkylhalide group and halogen are formed; Or

V does not exist;

W is NR ₄, O, S, S (O) or S (O) ₂Or

W does not exist;

X is N or CR ₅

Y is N or CR ₆

Z is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-2Alkyl amino, C _2-4Dialkyl amido, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _4-8Diacylamino group, C _2-6Dialkylformamide, C _1-4Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Dialkyl group sulfuryl amino, formoxyl, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group Methanamide, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, halogen, aryl, heterocyclic radical, heteroaryl, hydroxyl, hydroxyl amino, nitro and tetrazole radical are formed, wherein C _1-8Alkyl and C _1-5Acyl group replaces through 1,2,3 or 4 group separately according to circumstances, and described group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-4Alkyl formamides, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, amino, C _1-2Alkyl amino, C _2-4Dialkyl amido, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, formoxyl, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, halogen, hydroxyl, hydroxyl amino and nitro are formed; Or

Z is the group of formula (IA):

Wherein:

R ₇Be H, C _1-8Alkyl or C _3-6Cycloalkyl; And

R ₈Be H, nitro or nitrile;

Ar ₁Be aryl or heteroaryl, wherein each group is according to circumstances through R ₉-R ₁₃Replace;

R ₁Be selected from by H, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, amino, C _1-4Alkyl amino, C _2-8Dialkyl amido, Methanamide, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, C _2-6Dialkyl group sulfonamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl and hydroxyl are formed;

R ₂Be selected from by H, C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group, halogen, heteroaryl, hydroxyl and phenyl are formed; And C wherein _1-8Alkyl, heteroaryl and phenyl replace through 1 to 5 substituent group separately according to circumstances, and described substituent group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _3-6Cycloalkyl-C _1-3Alkylidene, C _3-6Cycloalkyl-C _1-3Inferior assorted alkyl, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _1-4Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Alkyl sulfide urea groups, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group, C _1-4The group that alkylhalide group sulfenyl, halogen, heterocyclic radical, hydroxyl, hydroxyl amino and nitro are formed; Or

R ₂Be-Ar ₂-Ar ₃, Ar wherein ₂And Ar ₃Be aryl or the heteroaryl that replaces through 1 to 5 substituent group according to circumstances separately independently, described substituent group is selected from by H, C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group, halogen, hydroxyl and nitro are formed; Or

R ₂Be the group of formula (IB):

Wherein:

R ₁₄Be C _1-8Alkyl or C _3-6Cycloalkyl; And R ₁₅Be F, Cl, Br or CN; Or

R ₂Be the group of formula (IC):

Wherein:

G is C=O, CR ₁₆R ₁₇, O, S, S (O), S (O) ₂R wherein ₁₆And R ₁₇Be H or C independently _1-8Alkyl; And

Ar ₄Be phenyl or the heteroaryl that replaces through 1 to 5 substituent group according to circumstances, described substituent group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, C _1-4Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Alkyl sulfide urea groups, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group, C _1-4The group that alkylhalide group sulfenyl, halogen, heteroaryl, hydroxyl, hydroxyl amino and nitro are formed;

R ₃Be H, C _1-8Alkyl, C _1-4Alkoxyl, halogen or hydroxyl;

R ₄Be H or C _1-8Alkyl;

R ₅And R ₆Be H, C independently _1-8Alkyl or halogen;

R ₉Be selected from by C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, amino, aryl sulfonyl, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkyl amido, C _2-6Dialkylformamide, C _2-6Dialkyl group sulfonamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group sulfenyl, heterocyclic radical, heterocyclic radical sulfonyl, heteroaryl, hydroxyl, nitro, C _4-7The group that oxo-cycloalkyl, phenoxy group, phenyl, sulfonamide and sulfonic acid are formed, and C wherein _1-5Acyl group, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl sulfonamide, alkyl sulphonyl, aryl sulfonyl, heteroaryl, phenoxy group and phenyl replace through 1 to 5 substituent group separately according to circumstances, and described substituent group is independently selected from by C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, heteroaryl, heterocyclic radical, hydroxyl, nitro and phenyl are formed; Or

R ₉Be the group of formula (ID):

Wherein:

" p " and " r " is 0,1,2 or 3 independently; And

R ₁₈Be H, C _1-5Acyl group, C _2-6Thiazolinyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, halogen, heteroaryl or phenyl, and wherein said heteroaryl and phenyl replace through 1 to 5 substituent group separately according to circumstances, and described substituent group is independently selected from by C _1-4Alkoxyl, amino, C _1-4Alkyl amino, C _2-6Alkynyl, C _2-8Dialkyl amido, halogen, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group and hydroxyl are formed; And

R ₁₀-R ₁₃Be independently selected from by C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, hydroxyl and nitro are formed; Or

Two adjacent R ₁₀-R ₁₁Group and Ar ₁Form 5 yuan, 6 yuan or 7 yuan of cycloalkyl, cycloalkenyl group or heterocyclic radicals together, wherein said 5 yuan, 6 yuan or 7 yuan of groups replace through halogen according to circumstances.

Diastereomer and optical isomer are also contained in the present invention, the for example mixture of enantiomer (comprising racemic mixture) and enantiomer and diastereomer individually, it is to produce because of the structural asymmetry in some chemical compound of the present invention.Realize that by the well-known the whole bag of tricks of professional in field under using the separation of individual isomers or the selectivity of individual isomers synthesize.

The particular instance of the GPR119 activator that discloses in No. PCT/US2004/001267th, international application case comprises following compound according to formula (I) (being referred to herein as the A1 group): [6-(4-benzenesulfonyl-piperidin-1-yl)-5-nitro-pyrimidine-4-yl]-(4-methane sulfonyl-phenyl)-amine; 4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-yl]-piperazine-1-yl }-ethyl acetate; (2-fluoro-phenyl)-5-nitro-6-[4-(pyridine-2-base sulfenyl)-piperidin-1-yl]-pyrimidine-4-yl }-amine; 1-[6-(4-imidazoles-1-base-phenoxy group)-5-nitro-pyrimidine-4-yl]-piperidine-4-ethyl formate; 1-[5-nitro-6-(4-[1,2,4] triazol-1-yl-phenoxy group)-pyrimidine-4-yl]-piperidine-4-ethyl formate; 6-[4-(4-fluoro-phenoxy group)-piperidin-1-yl]-5-nitro-pyrimidine-4-yl }-(4-methane sulfonyl-phenyl)-amine; 6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-1-yl]-5-nitro-pyrimidine-4-yl }-(4-methane sulfonyl-phenyl)-amine; 6-[4-(the 3-cyclopropyl-[1,2,4] oxadiazole-5-yls)-piperidines-1-yl]-5-nitro-pyrimidine-4-yl }-(4-methane sulfonyl-phenyl)-amine; (4-methane sulfonyl-phenyl)-(5-nitro-6-{4-[3-(3-trifluoromethyl-phenyl)-[1,2,4] oxadiazole-5-yl]-piperidin-1-yl }-pyrimidine-4-yl)-amine; 6-[4-(the 3-ethyl-[1,2,4] oxadiazole-5-yls)-piperidin-1-yl]-5-nitro-pyrimidine-4-yl }-(2-fluoro-phenyl)-amine; (2-fluoro-4-methane sulfonyl-phenyl)-6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-1-yl]-5-nitro-pyrimidine-4-yl }-amine; 6-[4-(the 3-ethyl-[1,2,4] oxadiazole-5-yls)-piperidin-1-yl]-5-nitro-pyrimidine-4-yl }-(2-fluoro-4-methane sulfonyl-phenyl)-amine; (4-methane sulfonyl-phenyl)-5-nitro-6-[4-(the 3-propyl group-[1,2,4] oxadiazole-5-yls)-piperidin-1-yl]-pyrimidine-4-yl }-amine; 6-[4-(3-cyclopropyl methyl-[1,2,4] oxadiazole-5-yls)-piperidin-1-yl]-5-nitro-pyrimidine-4-yl }-(4-methane sulfonyl-phenyl)-amine; (4-methane sulfonyl-phenyl)-5-nitro-6-[4-(pyridine-4-base oxygen base)-piperidin-1-yl]-pyrimidine-4-yl }-amine; (4-methane sulfonyl-phenyl)-5-nitro-6-[4-(pyrimidine-2-base oxygen base)-piperidin-1-yl]-pyrimidine-4-yl }-amine; 1-[6-(4-carbamyl ylmethyl-phenoxy group)-5-nitro-pyrimidine-4-yl]-piperidine-4-ethyl formate; 1-{6-[4-(1,3-dioxo-1,3-dihydro-iso-indoles-2-yl)-phenoxy group]-5-nitro-pyrimidine-4-yl }-piperidine-4-ethyl formate; 4 '-[4-(2-methoxycarbonyl group-acetyl group)-phenoxy group]-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6-[4-(2-methoxyl group-phenyl sulfenyl)-piperidin-1-yl]-5-nitro-pyrimidine-4-yl }-(4-[1,2,4] triazol-1-yl-phenyl)-amine; 4 '-(2-amino-4-ethane sulfonyl-phenoxy group)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 4 '-(4-imidazoles-1-base-phenoxy group)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; (4-methoxyl group-2-{5-nitro-6-[4-(pyridine-2-base sulfenyl)-piperidin-1-yl]-pyrimidine-4-yl oxygen base }-phenyl)-phenyl-ketone; 4-{4-[6-(4-cyclo propyl methoxy methyl-piperidines-1-yl)-5-nitro-pyrimidine-4-yl oxygen base]-phenyl }-Ding-2-ketone; 4-{4-[5-nitro-6-(4-propoxyl group methyl-piperidin-1-yl)-pyrimidine-4-yl oxygen base]-phenyl }-Ding-2-ketone; 4-{4-[6-(4-butoxymethyl-piperidin-1-yl)-5-nitro-pyrimidine-4-yl oxygen base]-phenyl }-Ding-2-ketone; 4-{4-[6-(4-isobutoxy methyl-piperidin-1-yl)-5-nitro-pyrimidine-4-yl oxygen base]-phenyl }-Ding-2-ketone; 1-[6-(benzo [1,3] dioxole-5-base is amino)-5-nitro-pyrimidine-4-yl]-piperidines-4-yl }-(4-fluoro-phenyl)-ketone; (2,3-, two fluoro-phenyl)-5-nitro-6-[4-(pyridine-2-base sulfenyl)-piperidin-1-yl]-pyrimidine-4-yl }-amine; (2,4-, two fluoro-phenyl)-5-nitro-6-[4-(pyridine-2-base sulfenyl)-piperidin-1-yl]-pyrimidine-4-yl }-amine; 1-{2-nitro-3-[4-(3-oxo-butyl)-phenoxy group]-phenyl }-piperidine-4-ethyl formate; 1-[6-(4-acetyl group-phenoxy group)-5-nitro-pyrimidine-4-yl]-piperidine-4-ethyl formate; 3 '-nitro-2 '-[4-(3-oxo-butyl)-phenoxy group]-3,4,5,6-tetrahydrochysene-2H-[1,4 '] bipyridyl-4-Ethyl formate; 4-(4-{5-nitro-6-[4-(pyridine-2-base sulfenyl)-piperidin-1-yl]-pyrimidine-4-yl oxygen base }-phenyl)-Ding-2-ketone; 4-(4-{5-nitro-6-[4-(2-trifluoromethyl-phenoxy group)-piperidin-1-yl]-pyrimidine-4-yl oxygen base }-phenyl)-Ding-2-ketone; 4-(4-{6-[4-(3-methyl-[1,2,4] oxadiazole-5-yl)-piperidin-1-yl]-5-nitro-pyrimidine-4-yl oxygen base }-phenyl)-Ding-2-ketone; 4-(2,4-, two fluoro-phenoxy groups)-5-nitro-6-[4-(pyridine-2-base sulfenyl)-piperidin-1-yl]-pyrimidine; 4-(4-{6-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-5-nitro-pyrimidine-4-yl oxygen base }-phenyl)-Ding-2-ketone; 4-(4-methane sulfonyl-phenoxy group)-5-nitro-6-[4-(pyridine-2-base sulfenyl)-cyclohexyl]-pyrimidine; 4-(4-methane sulfonyl-phenoxy group)-5-nitro-6-[4-(pyridine-4-base sulfenyl)-cyclohexyl]-pyrimidine; 4-(4-methane sulfonyl-phenoxy group)-5-nitro-6-(4-phenyl sulfenyl-cyclohexyl)-pyrimidine; 1-{6-[(benzo [1,3] dioxole-5-ylmethyl)-amino]-5-nitro-pyrimidine-4-yl }-piperidine-4-ethyl formate; 1-{6-[4-(1,1-dioxo-1 λ⁶- Thio-morpholin-4 - yl methyl) - phenyl amino] -5 - nitro - pyrimidin-4 - yl} - piperidin-4 - Ethyl; 1 - [6 - (4 - methanesulfonyl-- phenyl)-5 - nitro - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 1 - [6 - (4 - Dimethylsulfamoyl group - phenyl)-5 - nitro - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 1 - [6 - (3 - methoxy - phenyl amino Yl) -5 - nitro - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 1 - [6 - (2 - methoxy - phenyl)-5 - nitro - pyrimidin - yl] - Piperidin-4 - carboxylate; 1 - [6 - (4 - methanesulfonyl-- phenoxy) -5 - nitro - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 1 - {6 - [4 - (2 - methoxycarbonyl - acetyl) - phenoxy] -5 - nitro - pyrimidin-4 - yl} - piperidin-4 - carboxylate; 1 - [6 - (2 - amino- -4 - Ethanesulfonyl - phenoxy) -5 - nitro - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 1 - [6 - (2,5 - dimethoxy - phenyl Ammonia Yl) -5 - nitro - pyrimidin-4 - yl] - piperidin-4 - carboxylate; (4 - {5 - nitro-6 - [4 - (pyridin-2 - ylthio) - piperidine -1 - yl] - ethyl -4 - yl amino} - phenyl) - phenyl - methanone; 1 - [6 - (4 - cyclohexyl - phenyl)-5 - nitro - pyrimidin-4 - yl] - piperidin-4- - A Ethyl; 1 - [5 - nitro-6 - (4 - [1,2,4] triazol-1 - yl - phenylamino) - pyrimidin-4 - yl] - piperidin-4 - carboxylic acid ethyl ester; 1 - [5 - Nitro-6 - (4 - trifluoromethanesulfonyl - phenylamino) - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 1 - [5 - nitro-6 - (4 - [1 , 2,3] Thiadiazol-4 - yl - phenylamino) - pyrimidin-4 - yl] - piperidin-4 - carboxylate; [6 - (4 - ethoxy-methyl - piperidin-1 - yl) -5 - nitrate Yl - pyrimidin-4 - yl] - (4 - methanesulfonyl - phenyl) - amine; [5 - nitro-6 - (4 - propyl - piperidin-1 - yl) - pyrimidin-4 - Yl] - (4 - [1,2,4] triazol-1 - yl - phenyl) - amine; {5 - nitro-6 - [4 - (pyridin-2 - ylthio) - piperidine - 1 - yl] - pyrimidin-4 - Yl} - (4 - [1,2,4] triazol-1 - yl - phenyl) - amine; (2 - fluoro - phenyl) - {6 - [4 - (3 - methyl - [1, 2,4] oxadiazol-5 - yl) - piperidine-1 - Yl] -5 - nitro - pyrimidin-4 - yl} - amine; (4 - methanesulfonyl - phenyl) - {6 - [4 - (3 - methyl - [1,2,4] oxadiazole -5 - yl) - piperidine -1 - Yl] -5 - nitro - pyrimidin-4 - yl} - amine; {6 - [4 - (3 - methyl - [1,2,4] oxadiazol-5 - yl) - piperidine -1 - yl] -5 - nitro - pyrimidine -4 - Yl} - (4 - [1,2,4] triazol-1 - yl - phenyl) - amine; (4 - methanesulfonyl - phenyl) - {5 - nitro-6 - [4 - (pyridin-2 - yl thio) - Piperidin-1 - yl] - pyrimidin-4 - yl} - amine; (3 - methoxy - phenyl) - {5 - nitro-6 - [4 - (pyridin-2 - ylthio) - piperazine -1 - yl] - ethyl -4 - yl} - amine; 1 - [6 - (Benzo [1,3] dioxol-5 - yl)-5 - nitro - pyrimidin-4 - yl] - piperidine -4 - formic acid Ester; 1 - [6 - (2 - fluoro - phenyl)-5 - nitro - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 1 - [6 - (3 - fluoro - phenyl ylamino) -5 - Nitro - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 1 - [6 - (3,4 - dihydro-2H-benzo [b] [1,4] dioxa Zhuo -7 - ylamino) -5 - Nitro - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 1 - {6 - [4 - (morpholin-4 - sulfonyl) - phenyl amino] -5 - nitro - pyrimidin-4 - Yl} - piperidin-4 - carboxylate; Benzo [1,3] dioxol-5 - yl - [5 - nitro-6 - (4 - propyl - piperidin - yl) - pyrimidine -4 - Yl] - amine; (4 - fluoro - phenyl) - {1 - [5 - nitro-6 - (4 - [1,2,4] triazol-1 - yl - phenylamino) - pyrimidin-4 - yl] - piperidin-4 - Yl} - methanone; [5 - nitro-6 - (4 - phenylthio - piperidin-1 - yl) - pyrimidin-4 - yl] - (4 - [1,2,4] triazol - 1 - yl - phenyl) - amine; (4 - Fluoro - phenyl) - {1 - [6 - (2 - fluoro - phenyl)-5 - nitro - pyrimidin-4 - yl] - piperidin-4 - yl} - methanone; (4 - methanesulfonamide acyl - benzene Yl) - [5 - nitro-6 - (4 - phenylthio - piperidin-1 - yl) - pyrimidin-4 - yl] - amine; (4 - methanesulfonyl - phenyl) - {5 - Nitro -6 - [4 - (pyridin-2 - yloxy) - piperidin-1 - yl] - pyrimidin-4 - yl} - amine; (4 - methanesulfonyl - phenyl) - {5 - nitro - 6 - [4 - (topiramate -4 - ylthio) - piperidin-1 - yl] - pyrimidin-4 - yl} - amine; (4 - methanesulfonyl - phenyl) - {6 - [4 - (4 - methoxy - phenyl sulfide Yl) - piperidin-1 - yl] -5 - nitro - pyrimidin-4 - yl} - amine China; - methoxy - phenyl) - {5 - nitro-6 - [4 - (pyridin-2 - ylthio) - piperazine -1 - yl] - pyrimidin-4 - yl} - amine; (4 - methanesulfonyl - phenyl) - (5 - nitro-6 - {4 - [3 - (3 - (trifluoromethyl) - phenyl yl) - [1,2,4] Oxadiazol-5 - yl] - piperidin-1 - yl} - pyrimidin-4 - yl) - amine; {6 - [4 - (3 - ethyl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl] -5 - Nitro - pyrimidin-4 - yl} - (4 - methanesulfonyl - phenyl) - amine; (6 - {4 - [5 - (4 - fluoro - phenyl) - [1,3,4] oxadiazole oxazol-2 - yl] - piperidine -1 - Yl} -5 - nitro - pyrimidin-4 - yl) - (4 - methanesulfonyl - phenyl) - amine; (4 - methanesulfonyl - phenyl) - [5 - nitro-6 - (4 - topiramate -2 - yl methyl - piperidin-1 - yl) - pyrimidin-4 - yl] - amine; 1 - {6 - [4 - (2,5 - dioxo - imidazolidin-4 - yl) - phenoxy]-5-nitro - - Pyrimidin-4 - yl} - piperidin-4 - carboxylate; 1 - [5 - nitro-6 - (4 - propionyl - phenoxy) - pyrimidin-4 - yl] - piperidin-4 - ethyl formate Ester; 1 - [5 - nitro-6 - (4 - [1,2,3] thiadiazol-4 - yl - phenoxy) - pyrimidin-4 - yl] - piperidin-4 - carboxylic acid ethyl ester ; 1 - [6 - [4 - (3 - Oxo - butyl) - phenoxy] -5 - (2,2,2 - trifluoro - acetylamino) - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 1 - [6 - (2 - phenyl Formyl-5 - methoxy - phenoxy) -5 - nitro - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 3'-nitro-4'-[4 - (3 - oxo - Ding Yl) - phenoxy] -3,4,5,6 - tetrahydro-2H-[1,2 ']-4-linked - Ethyl; 1 - [6 - (4 - dimethylsulfamoyl group - Phenyl Yl) -5 - nitro - pyrimidin-4 - yl] - piperidin-4 - carboxylate; 1 - {6 - [4 - (4,5 - dichloro - imidazol-1 - yl) - phenylamino ] -5 - nitro- - Pyrimidin-4 - yl} - piperidin-4 - carboxylate; Benzo [1,3] dioxol-5 - yl - {5 - nitro-6 - [4 - (pyridin - 2 - group sulfide Yl) - piperidin-1 - yl] - pyrimidin-4 - yl} - amine; (4 - fluoro - phenyl) - {1 - [6 - (2 - fluoro - phenyl)-5 - nitro - pyrimidin-4 - yl] - piperazine -4 - yl} - methanone; (2,5 - difluoro - phenyl) - {5 - nitro-6 - [4 - (pyridin-2 - ylthio) - piperidin-1 - yl] - pyrimidin-4 - yl} - amine; 1 - {5 - nitro-6 - [4 - (3 - oxo - butyl) - phenoxy] - pyrimidin-4 - yl} - piperidin-4 - carboxylic acid ethyl ester; 4 - [4 - ( 3 - isopropyl- - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl] -6 - (4 - methanesulfonyl-- phenoxy) - pyrimidine-5 - carbonitrile; 5 - [1 , 3] dioxolan -2 - Yl -4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl] -6 - (4 - methanesulfonyl - phenoxy) - pyrimidine; 4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl] -6 - (4 - methanesulfonyl-- phenoxy) - pyrimidine-5 - formaldehyde; 5 - [1,3] dioxolan-2 - yl -4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl ] -6 - (4 - [1,2,3] thiadiazol- -4 - Yl - phenoxy) - pyrimidine; 4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl] -6 - (4 - [1,2,3] thiadiazol-4 - Yl - phenoxy) - pyrimidin-5 - formaldehyde; 4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl] -6 - (4 - [1,2,3] thiadiazol -4 - yl - phenoxy) - pyrimidine-5 - carboxylic acid; [4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl] -6 - (4 - [1,2,3] Thiadiazol-4 - yl - phenoxy) - pyrimidin-5 - yl] - methanol; [4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - Yl] -6 - (4 - [1,2,3] thiadiazol-4 - yl - phenoxy) - pyrimidin-5 - yl methyl] - dimethyl - amine; 4 - [4 - (3 - isopropyl - [1,2,4] Oxadiazol-5 - yl) - piperidin-1 - yl] -6 - (4 - methyl thio - phenylamino) - pyrimidine-5 - carbonitrile; 4 - [4 - (3 - isopropyl- - [1,2,4] Oxadiazol-5 - yl) - piperidin-1 - yl] -6 - (4 - methylsulfinyl - phenylamino) - pyrimidine-5 - carbonitrile; (4 - methanesulfonyl - benzene Yl) - {5 - nitro-6 - [4 - (4 - (Trifluoromethoxy) - phenoxy) - piperidin-1 - yl] - pyrimidin-4 - yl} - amine; 4 - [4 - (3 - isopropyl - [1,2,4] Oxadiazol-5 - yl) - piperidin-1 - yl] -6 - (4 - methanesulfonyl-- phenylamino) - pyrimidine-5 - carbonitrile; 1 - {1 - [6 - (2 - fluoro- -4 - methane Sulfonyl - phenyl)-5 - nitro - pyrimidin-4 - yl] - piperidin-4 - yl} - hexan-1 - one; 1 - {1 - [6 - (4 - methanesulfonyl - benzene Ammonia Yl) -5 - nitro - pyrimidin-4 - yl] - piperidin-4 - yl} - hexan-1 - one; {6 - [4 - (3 - tert-butyl - [1,2,4] oxadiazol-5 - yl) - piperidine-1 - Yl] -5 - nitro - pyrimidin-4 - yl} - (2 - fluoro-4 - methanesulfonyl-- phenyl) - amine; {6 - [4 - (3 - tert-butyl - [1,2, 4] oxadiazol-5 - Yl) - piperidin-1 - yl] -5 - nitro - pyrimidin-4 - yl} - (4 - methanesulfonyl - phenyl) - amine; [6 - (4 - benzofuran-2 - yl - piperidin-1 - Yl) -5 - nitro - pyrimidin-4 - yl] - (4 - methanesulfonyl - phenyl) - amine and 5 - nitro - 4 - (5 - phenyl - [1,3,4] oxadiazole oxazol-2 - yl sulfide Yl) -6 - [4 - (pyridin-2 - ylthio) - piperidin-1 - yl] - pyrimidine. ...

The case description of GPR119 agonist in international application case PCT/US2004/005555 number (open) with WO04/076413, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/US2004/005555 number is formula (II) chemical compound:

(II)

Wherein:

U is N or CR ₁

D is O, S, S (O), S (O) ₂, CR ₂R ₃Or NR ₂

V is selected from by C _1-3Alkylidene, ethynylene and C _1-2The group that inferior assorted alkyl is formed, described group replaces through 1 to 4 substituent group according to circumstances, and described substituent group is selected from by C _1-3Alkyl, C _1-4Alkoxyl, carboxyl, cyano group, C _1-3The group that alkylhalide group and halogen are formed; Or V does not exist;

W is-S (O) ₂NR ₄-,-NR ₄-,-O-,-S-,-S (O)-,-S (O) ₂-; Or W does not exist;

X is N or CR ₅

Y is N or CR ₆

Z is selected from by H, C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-6Alkyl, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _4-8Diacylamino group, C _1-4Dialkylformamide, C _1-4Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Dialkyl group sulfuryl amino, formoxyl, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group Methanamide, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, halogen, aryl, heteroaryl, hydroxyl, hydroxyl amino, nitro and tetrazole radical are formed; Or

Z is the group of formula (IIA):

Wherein:

R ₇Be H, C _1-6Alkyl or C _3-6Cycloalkyl; And

R ₈Be H, nitro or cyano group;

Ar ₁Be according to circumstances through R ₉, R ₁₀, R ₁₁, R ₁₂And R ₁₃The aryl or the heteroaryl that replace;

R ₁, R ₅And R ₆Be independently selected from by H, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, amino, C _1-4Alkyl amino, C _2-8Dialkyl amido, Methanamide, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, C _2-6Dialkyl group sulfonamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, hydroxyl and nitro are formed;

R ₂Be selected from by H, C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group, halogen, heteroaryl, hydroxyl and phenyl are formed; And C wherein _1-8Alkyl, heteroaryl and phenyl replace through 1 to 5 substituent group according to circumstances, and described substituent group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _3-6Cycloalkyl-C _1-3Inferior assorted alkyl, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _1-4Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Alkyl sulfide urea groups, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group, C _1-4The group that alkylhalide group sulfenyl, halogen, heterocyclic radical, hydroxyl, hydroxyl amino and nitro are formed; Or

R ₂Be-Ar ₂-Ar ₃, Ar wherein ₂And Ar ₃Be aryl or the heteroaryl that replaces through 1 to 5 substituent group according to circumstances independently, described substituent group is selected from by H, C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group, halogen, hydroxyl and nitro are formed; Or

R ₂Be the group of formula (IIB):

Wherein:

R ₁₄Be C _1-8Alkyl or C _3-6Cycloalkyl; And R ₁₅Be F, Cl, Br or CN; Or

R ₂Be the group of formula (IIC):

Wherein:

R ₃Be H, C _1-8Alkyl, C _1-4Alkoxyl or hydroxyl;

R ₄Be H or C _1-8Alkyl;

R ₉Be selected from by C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, amino, aryl sulfonyl, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group sulfenyl, heterocyclic radical, heterocyclic radical sulfonyl, heteroaryl, hydroxyl, nitro, C _4-7The group that oxo-cycloalkyl, phenoxy group, phenyl, sulfonamide and sulfonic acid are formed, and C wherein _1-5Acyl group, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl sulfonamide, alkyl sulphonyl, aryl sulfonyl, heteroaryl, phenoxy group and phenyl replace through 1 to 5 substituent group according to circumstances, and described substituent group is independently selected from by C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, heteroaryl, heterocyclic radical, hydroxyl, nitro and phenyl are formed; Or

R ₉Be the group of formula (IID):

Wherein:

" p " and " r " is 0,1,2 or 3 independently; And

R ₁₈Be H, C _1-5Acyl group, C _2-6Thiazolinyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, halogen, heteroaryl or phenyl, and wherein said heteroaryl or phenyl replace through 1 to 5 substituent group according to circumstances, and described substituent group is independently selected from by C _1-4Alkoxyl, C _1-8Alkyl, amino, C _1-4Alkyl amino, C _2-6Alkynyl, C _2-8Dialkyl amido, halogen, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group and hydroxyl are formed; And

R ₁₀-R ₁₃Be independently selected from by C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, hydroxyl and nitro are formed; Or

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/005555 number comprises following chemical compound according to formula (II) (being referred to herein as the B1 group): 6 '-[4-(2-methoxycarbonyl group-acetyl group)-phenoxy group]-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 1-[4-(4-acetyl group-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-6 '-Ji oxygen base)-phenyl]-ethyl ketone; 6 '-[4-(4-hydroxyl-benzenesulfonyl)-phenoxy group]-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-(4-imidazoles-1-base-phenoxy group)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-(4-benzoyl-phenoxy group)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-[4-(2-methoxyl group-ethyl)-phenoxy group]-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-(4-cyclopenta-phenoxy group)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-(4 '-cyano group-xenyl-4-base oxygen base)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 3 '-nitro-6 '-(4-sulfo group-phenoxy group)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 3 '-nitro-6 '-(4-pyrroles-1-base-phenoxy group)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-(4-carbamoyl-phenoxy group)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 3 '-nitro-6 '-(4-[1,2,4] triazol-1-yl-phenoxy group)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-(2-amino-4-ethane sulfonyl-phenoxy group)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 3 '-nitro-6 '-[4-(4-oxo-cyclohexyl)-phenoxy group]-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-(4 '-methoxyl group-xenyl-4-base oxygen base)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 3 '-nitro-6 '-(4-[1,2,3] thiadiazoles-4-base-phenoxy group)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-[4-(1,3-dioxo-1,3-dihydro-iso-indoles-2-yl)-phenoxy group]-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-[4-(2,5-dioxo-imidazolidine-4-yl)-phenoxy group]-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 3 '-nitro-6 '-[4-(3-oxo-butyl)-phenoxy group]-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 3-[4-(3 '-nitro-4-propyl group-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-6 '-Ji oxygen base)-phenyl]-3-oxo-methyl propionate; 4-[4-(3 '-nitro-4-propyl group-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-6 '-Ji oxygen base)-phenyl]-Ding-2-ketone; 4-{4-[3 '-nitro-4-(pyridine-2-base sulfenyl)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-6 '-Ji oxygen base]-phenyl }-Ding-2-ketone; With 3 '-nitro-4-(pyridine-2-base sulfenyl)-6 '-(4-[1,2,4] triazol-1-yl-phenoxy group)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/005555 number comprises following chemical compound according to formula (II) (being referred to herein as the B2 group): 1-[5-(4-benzoyl-phenoxy group)-2-nitro-phenyl]-piperidine-4-ethyl formate; 1-{5-[4-(2-methoxycarbonyl group-acetyl group)-phenoxy group]-2-nitro-phenyl }-piperidine-4-ethyl formate; 1-[5-(2-amino-4-ethane sulfonyl-phenoxy group)-2-nitro-phenyl]-piperidine-4-ethyl formate; 1-{2-nitro-5-[4-(3-oxo-butyl)-phenoxy group]-phenyl }-piperidine-4-ethyl formate; 4-{4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-Ding-2-ketone; 1-{4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-ethyl ketone; 3-{4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-3-oxo-methyl propionate; 5-ethane sulfonyl-2-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-aniline; 4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-phenyl-ketone; 1-{4-nitro-3-[4-(3-oxo-butyl)-phenoxy group]-phenyl }-piperidine-4-ethyl formate; 4-{4-[2-nitro-5-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-Ding-2-ketone; 1-[3-(4-benzoyl-phenoxy group)-4-nitro-phenyl]-piperidine-4-ethyl formate; 4-[2-nitro-5-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-phenyl-ketone; 1-{5-[4-(2-carboxyl-ethyl)-phenoxy group]-2-nitro-phenyl }-piperidine-4-ethyl formate; 1-{5-[4-(2-carboxyl-2-oxo-ethyl)-phenoxy group]-2-nitro-phenyl }-piperidine-4-ethyl formate; 1-[2-nitro-5-(4-vinyl-phenoxy group)-phenyl]-piperidine-4-ethyl formate; 3-{4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-propanoic acid; 3-{4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-2-oxo-propanoic acid; 1-[2-nitro-5-(4-vinyl-phenoxy group)-phenyl]-4-propyl group-piperidines; 1-{4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-Ding-1-ketone; 1-{4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-penta-1-ketone; 1-{4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-oneself-1-ketone; 4-{4-[3-(4-methoxy-piperidines-1-yl)-4-nitro-phenoxy group]-phenyl }-Ding-2-ketone; 1-{4-[3-(4-methoxy-piperidines-1-yl)-4-nitro-phenoxy group]-phenyl }-ethyl ketone; 4-[3-(4-methoxy-piperidines-1-yl)-4-nitro-phenoxy group]-phenyl }-phenyl-ketone; 2-(the 3-methyl-[1,2,4] oxadiazole-5-yls)-1-{4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-ethyl ketone; 4-(4-{3-[4-(3-methyl-[1,2,4] oxadiazole-5-yl)-piperidines-1-yl]-4-nitro-phenoxy group }-phenyl)-Ding-2-ketone; 4-(4-{4-nitro-3-[4-(pyridine-2-base sulfenyl)-piperidines-1-yl]-phenoxy group }-phenyl)-Ding-2-ketone; 2-{1-[2-nitro-5-(4-[1,2,4] triazol-1-yl-phenoxy group)-phenyl]-the piperidin-4-yl sulfenyl }-pyridine; 2-methyl-5-{4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-phenyl }-2H-pyrazoles-3-alcohol; 2-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-5-trifluoromethyl-pyridine; 5-bromo-2-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenoxy group]-pyridine; 1-(4-{4-nitro-3-[4-(pyridine-2-base sulfenyl)-piperidines-1-yl]-phenoxy group }-phenyl)-ethyl ketone; 2-{1-[5-(4-methane sulfonyl-phenoxy group)-2-nitro-phenyl]-the piperidin-4-yl sulfenyl }-pyridine; 1-{5-[4-(the 5-methyl-[1,3,4] oxadiazole-2-yls)-phenoxy group]-2-nitro-phenyl }-4-propyl group-piperidines; 1-{5-[3-(the 3-methyl-[1,2,4] oxadiazole-5-yls)-phenoxy group]-2-nitro-phenyl }-4-propyl group-piperidines.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/005555 number comprises following chemical compound according to formula (II) (being referred to herein as the B3 group): 5-bromo-1-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenyl]-the 1H-pyridin-2-ones.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/005555 number comprises following chemical compound according to formula (II) (being referred to herein as the B4 group): 6 '-benzenesulfonyl amino-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-(benzenesulfonyl-methyl-amino)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-(benzenesulfonyl-butyl-amino)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-(5-ethane sulfonyl-2-hydroxyl-phenyl amino)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 6 '-(2-bromo-4-trifluoromethyl-benzenesulfonyl amino)-3 '-nitro-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-Ethyl formate; 4-[3 '-nitro-4-(pyridine-2-base sulfenyl)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-6 '-Ji amino]-phenyl-phenyl-ketone and [3 '-nitro-4-(pyridine-2-base sulfenyl)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-6 '-yl]-(4-[1,2,4] triazol-1-yl-phenyl)-amine.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/005555 number comprises following chemical compound according to formula (II) (being referred to herein as the B5 group): 1-[5-(4-benzoyl-phenyl amino)-2-nitro-phenyl]-piperidine-4-ethyl formate and { 4-[4-nitro-3-(4-propyl group-piperidines-1-yl)-phenyl amino]-phenyl }-phenyl-ketone.

The case description of GPR119 agonist in international application case PCT/US2004/022327 number (open) with WO05/007647, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/US2004/022327 number is formula (III) chemical compound:

Wherein:

A and B are the C that replaces through 1 to 4 substituent group according to circumstances independently of one another _1-3Alkylidene, described substituent group is selected from by C _1-3Alkyl, C _1-4Alkoxyl, carboxyl, cyano group, C _1-3The group that alkylhalide group and halogen are formed;

D is O, S, S (O), S (O) ₂, CR ₂R ₃Or N-R ₂

E is N, C or CR ₄

When E is N or CR ₄The time,

Be singly-bound, or when E is C,

Be two keys;

V ₁Be selected from by C _1-3Alkylidene, ethynylene and C _1-2The group that inferior assorted alkyl is formed, described group replaces through 1 to 4 substituent group according to circumstances, and described substituent group is selected from by C _1-3Alkyl, C _1-4Alkoxyl, carboxyl, cyano group, C _1-3The group that alkylhalide group and halogen are formed; Or V ₁It is key;

V ₂Be C _3-6Cycloalkylidene or C _1-3Alkylidene, wherein each group replaces through 1 to 4 substituent group according to circumstances, and described substituent group is selected from by C _1-3Alkyl, C _1-4Alkoxyl, carboxyl, cyano group, C _1-3The group that alkylhalide group and halogen are formed; Or V ₂It is key;

W is NR ₅, O, S, S (O) or S (O) ₂Or W does not exist;

Q is NR ₆, O, S, S (O) or S (O) ₂

X is N or CR ₇

Y is N or CR ₈

Z is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-2Alkyl amino, C _2-4Dialkyl amido, amidino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _4-8Diacylamino group, C _2-6Dialkylformamide, C _2-6Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _2-6Dialkyl group sulfuryl amino, formoxyl, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group Methanamide, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, halogen, aryl, heterocyclic radical, heteroaryl, hydroxyl, hydroxy formamidine base, hydroxyl amino, nitro and tetrazole radical are formed, wherein C _1-8Alkyl, C _3-7Cycloalkyl and heterocyclic radical replace through 1,2,3 or 4 group separately according to circumstances, and described group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-7Alkyl, C _1-4Alkyl formamides, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, amino, C _1-2Alkyl amino, C _2-4Dialkyl amido, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, formoxyl, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, halogen, hydroxyl, hydroxyl amino and nitro are formed, and wherein said C _1-7Alkyl replaces through amino according to circumstances; Or

Z is the group of formula (IIIA):

Wherein:

R ₉Be H, C _1-8Alkyl or C _3-7Cycloalkyl; And

R ₁₀Be H, nitro or nitrile;

Ar ₁Be aryl or heteroaryl, it is separately according to circumstances through R ₁₁, R ₁₂, R ₁₃, R ₁₄And R ₁₅Replace; R wherein ₁₁Be selected from by C _1-5Acyl group, C _1-6Acyl group sulfonamide, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl amino, C _1-6Alkyl formamides, C _1-4Alkylthio Methanamide, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, aryl sulfonyl, amidino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _3-7Cycloalkyl oxy, C _2-6Dialkyl amido, C _2-6Dialkylformamide, C _2-6Dialkyl group thioformamide, guanidine radicals, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group sulfenyl, heterocyclic radical, heterocyclic radical-oxygen base, heterocyclic radical sulfonyl, heterocyclic radical-carbonyl, heteroaryl, heteroaryl carbonyl, hydroxyl, nitro, C _4-7The group that oxo-cycloalkyl, phenoxy group, phenyl, sulfonamide, sulfonic acid and mercaptan are formed, and C wherein _1-5Acyl group, C _1-6Acyl group sulfonamide, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl amino, C _1-6Alkyl sulfonamide, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, aryl sulfonyl, amidino, C _2-6Dialkyl amido, heterocyclic radical, heterocyclic radical-carbonyl, heteroaryl, phenoxy group and phenyl replace through 1 to 5 substituent group according to circumstances, and described substituent group is independently selected from by C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-7Alkyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _3-7Cycloalkyl oxy, C _2-6Dialkyl amido, C _2-6Dialkylformamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, heteroaryl, heterocyclic radical, hydroxyl, nitro, phenyl and phosphonato are formed, wherein said C _1-7Alkyl and C _1-4Alkyl formamides replaces through 1 to 5 substituent group separately according to circumstances, and described substituent group is selected from by C _1-4The group that alkoxyl and hydroxyl are formed; Or

R ₁₁Be the group of formula (IIIB):

Wherein:

" p " and " r " is 0,1,2 or 3 independently of one another; And R ₁₆Be H, C _1-5Acyl group, C _2-6Thiazolinyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _2-6Dialkylformamide, halogen, heteroaryl or phenyl, and wherein said heteroaryl or phenyl replace through 1 to 5 substituent group according to circumstances, and described substituent group is independently selected from by C _1-4Alkoxyl, amino, C _1-4Alkyl amino, C _2-6Alkynyl, C _2-8Dialkyl amido, halogen, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group and hydroxyl are formed; And

R ₁₂, R ₁₃, R ₁₄And R ₁₅Be selected from by C independently of one another _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _2-6Dialkylformamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, hydroxyl and nitro are formed; Or

Two are selected from by R ₁₂, R ₁₃, R ₁₄And R ₁₅The adjacent group of the group that forms forms and Ar with the atom that it connected ₁Condensed 5 yuan, 6 yuan or 7 yuan of cycloalkyl, cycloalkenyl group or heterocyclic radicals, wherein said 5 yuan, 6 yuan or 7 yuan of groups replace through halogen according to circumstances;

R ₁, R ₇And R ₈Be selected from independently of one another by H, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, amino, C _1-4Alkyl amino, C _2-8Dialkyl amido, Methanamide, cyano group, C _3-7Cycloalkyl, C _2-6Dialkylformamide, C _2-6Dialkyl group sulfonamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl and hydroxyl are formed;

R ₂Be selected from by C _1-8Alkyl, amino, aryl, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group, halogen, heteroaryl and hydroxyl are formed; And C wherein _1-8Alkyl, aryl or heteroaryl replace through 1 to 5 substituent group according to circumstances, and described substituent group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _3-6Cycloalkyl-C _1-3Inferior assorted alkyl, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _2-6Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Alkyl sulfide urea groups, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group, C _1-4The group that alkylhalide group sulfenyl, halogen, heterocyclic radical, hydroxyl, hydroxyl amino and nitro are formed; Or

R ₂Be-Ar ₂-Ar ₃, Ar wherein ₂And Ar ₃Be aryl or the heteroaryl that replaces through 1 to 5 substituent group according to circumstances independently of one another, described substituent group is selected from by H, C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, amino, C _1-4Alkyl amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group, halogen, hydroxyl and nitro are formed; Or

R ₂Be the group of formula (IIIC):

Wherein:

R ₁₇Be H, C _1-8Alkyl, C _3-7Cycloalkyl, aryl, heteroaryl or OR ₁₉And R ₁₈Be F, Cl, Br, CN or NR ₂₀R ₂₁R wherein ₁₉Be H, C _1-8Alkyl or C _3-7Cycloalkyl, and R ₂₀And R ₂₁Be H, C independently of one another _1-8Alkyl, C _3-7Cycloalkyl, aryl or heteroaryl; Or

R ₂Be the group of formula (IIID):

(IIID)

Wherein:

I) when D be CR ₂R ₃The time, G is-C (O)-,-C (O) NR ₂₃-,-C (O) O-,-OC (O) NR ₂₃-,-NR ₂₃C (O) O-,-OC (O)-,-C (S)-,-C (S) NR ₂₃-,-C (S) O-,-OC (S)-,-CR ₂₃R ₂₄-,-O-,-S-,-S (O)-or-S (O) ₂-, or

Ii) working as D is NR ₂The time, G is-CR ₂₃R ₂₄C (O)-,-C (O)-,-CR ₂₃R ₂₄C (O) NR ₂₅-,-C (O) NR ₂₃-,-C (O) O-,-C (S)-,-C (S) NR ₂₃-,-C (S) O-,-CR ₂₃R ₂₄-,-S (O) ₂-or key,

R wherein ₂₃, R ₂₄And R ₂₅Be H or C independently of one another _1-8Alkyl; And R ₂₂Be H, C _1-8Alkyl, C _2-6Alkynyl, C _3-7Cycloalkyl, phenyl, heteroaryl or heterocyclic radical, described group replace through 1 to 5 substituent group separately according to circumstances, and described substituent group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-7Alkyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _2-6Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Alkyl sulfide urea groups, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group, C _1-4The group that alkylhalide group sulfenyl, halogen, heteroaryl, heterocyclic radical, hydroxyl, hydroxyl amino, nitro, phenyl, phenoxy group and sulfonic acid are formed, wherein said C _1-7Alkyl, heteroaryl, phenyl and phenoxy group replace through 1 to 5 substituent group separately according to circumstances, and described substituent group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _2-6Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Alkyl sulfide urea groups, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group, C _1-4The group that alkylhalide group sulfenyl, halogen, heterocyclic radical, hydroxyl, hydroxyl amino and nitro are formed;

R ₃Be H, C _1-8Alkyl, C _1-4Alkoxyl or hydroxyl; And

R ₄, R ₅And R ₆Be H, C independently of one another _1-8Alkyl or C _3-7Cycloalkyl, wherein said C _1-8Alkyl is according to circumstances through C _1-4Alkoxyl, C _3-7Cycloalkyl or heteroaryl replace.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022327 number comprises following chemical compound according to formula (III) (being referred to herein as the C1 group): 3-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen ylmethyl]-pyrrolidine-1-t-butyl formate; 4-[5-cyano group-6-(6-methyl sulfenyl-pyridin-3-yl amino)-pyrimidine-4-base oxygen base]-piperidines-1-t-butyl formate; 4-[5-cyano group-6-(6-methane sulfonyl-pyridin-3-yl amino)-pyrimidine-4-base oxygen base]-piperidines-1-t-butyl formate; [6-(1-hexyl-piperidin-4-yl oxygen base)-5-nitro-pyrimidine-4-yl]-(4-methane sulfonyl-phenyl)-amine; [6-(1-cyclopropyl methyl-piperidin-4-yl oxygen base)-5-nitro-pyrimidine-4-yl]-(4-methane sulfonyl-phenyl)-amine; 4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-piperidines-1-formic acid 2-isopropyl-5-methyl-cyclohexyl ester; 4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-piperidines-1-yl }-pyridin-3-yl-ketone; (2-chloro-pyridin-3-yl)-4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-piperidines-1-yl }-ketone; 4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-piperidines-1-yl }-pyridine-2-base-ketone; (4-methane sulfonyl-phenyl)-[6-(1-methane sulfonyl-piperidin-4-yl oxygen base)-5-nitro-pyrimidine-4-yl]-amine; (4-methane sulfonyl-phenyl)-5-nitro-6-[1-(propane-1-sulfonyl)-piperidin-4-yl oxygen base]-pyrimidine-4-yl }-amine; 6-[1-(butane-1-sulfonyl)-piperidin-4-yl oxygen base]-5-nitro-pyrimidine-4-yl }-(4-methane sulfonyl-phenyl)-amine; (4-methane sulfonyl-phenyl)-5-nitro-6-[1-(thiophene-2-sulfonyl)-piperidin-4-yl oxygen base]-pyrimidine-4-yl }-amine; (4-methane sulfonyl-phenyl)-6-[1-(1-methyl isophthalic acid H-imidazoles-4-sulfonyl)-piperidin-4-yl oxygen base]-5-nitro-pyrimidine-4-yl }-amine; 6-[1-(2,4-dimethyl-thiazole-5-sulfonyl)-piperidin-4-yl oxygen base]-5-nitro-pyrimidine-4-yl }-(4-methane sulfonyl-phenyl)-amine; 4-[5-cyano group-6-(3-fluoro-4-methane sulfonyl-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-t-butyl formate; 4-[6-(2-fluoro-4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-piperidines-1-t-butyl formate; 4-[5-cyano group-6-(4-methane sulfonyl-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-t-butyl formate; 4-[6-(6-methane sulfonyl-pyridin-3-yl amino)-5-nitro-pyrimidine-4-base oxygen base]-piperidines-1-t-butyl formate; 4-[5-acetyl group-6-(6-methane sulfonyl-pyridin-3-yl amino)-pyrimidine-4-base oxygen base]-piperidines-1-t-butyl formate; 4-[5-amino-6-(2-fluoro-4-methane sulfonyl-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-t-butyl formate; 4-[5-cyano group-6-(4-methane sulfonyl-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-cyano group-6-(4-methane sulfonyl-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-Ethyl formate; 4-[5-cyano group-6-(4-methane sulfonyl-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-Tetryl formate.; 4-(4-methane sulfonyl-phenyl amino)-6-[1-(tetrahydrochysene-furan-2-carbonyl)-piperidin-4-yl oxygen base]-pyrimidine-5-formonitrile HCN; 4-[1-(3,3-dimethyl-2-oxo-butyl)-piperidin-4-yl oxygen base]-6-(4-methane sulfonyl-phenyl amino)-pyrimidine-5-formonitrile HCN; 4-(4-methane sulfonyl-phenyl amino)-6-[1-(pyridine-3-carbonyl)-piperidin-4-yl oxygen base]-pyrimidine-5-formonitrile HCN; 4-(1-formoxyl-piperidin-4-yl oxygen base)-6-(4-methane sulfonyl-phenyl amino)-pyrimidine-5-formonitrile HCN and 4-(4-methane sulfonyl-phenyl amino)-6-[1-(pyridine-2-carbonyl)-piperidin-4-yl oxygen base]-pyrimidine-5-formonitrile HCN.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022327 number comprises following chemical compound according to formula (III) (being referred to herein as the C2 group): 4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-piperidines-1-t-butyl formate; (4-methane sulfonyl-phenyl)-[5-nitro-6-(piperidin-4-yl oxygen base)-pyrimidine-4-yl]-amine; 1-{4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-piperidines-1-yl }-3,3-dimethyl-Ding-1-ketone; (4-methane sulfonyl-phenyl)-[5-nitro-6-(1-pyridine-2-ylmethyl-piperidin-4-yl oxygen base)-pyrimidine-4-yl]-amine; (4-methane sulfonyl-phenyl)-[5-nitro-6-(1-pyridin-3-yl methyl-piperidin-4-yl oxygen base)-pyrimidine-4-yl]-amine; 6-[1-(3,3-dimethyl-butyl)-piperidin-4-yl oxygen base]-5-nitro-pyrimidine-4-yl }-(4-methane sulfonyl-phenyl)-amine; (4-methane sulfonyl-phenyl)-6-[1-(3-methyl-butyl)-piperidin-4-yl oxygen base]-5-nitro-pyrimidine-4-yl }-amine; (4-methane sulfonyl-phenyl)-[5-nitro-6-(3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4-base oxygen base)-pyrimidine-4-yl]-amine; 4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-piperidines-1-Ethyl formate; 1-{4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-piperidines-1-yl }-3,3-dimethyl-Ding-2-ketone; 6-[1-(2-ethyoxyl-ethyl)-piperidin-4-yl oxygen base]-5-nitro-pyrimidine-4-yl }-(4-methane sulfonyl-phenyl)-amine; 4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen ylmethyl]-piperidines-1-t-butyl formate; 4-{2-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-ethyl }-piperidines-1-t-butyl formate; 3-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen base]-pyrrolidine-1-t-butyl formate and 3-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base oxygen ylmethyl]-pyrrolidine-1-t-butyl formate.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022327 number comprises following chemical compound according to formula (III) (being referred to herein as the C3 group): 4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base is amino]-piperidines-1-t-butyl formate; N-(4-methane sulfonyl-phenyl)-5-nitro-N '-piperidin-4-yl-pyrimidine-4, the 6-diamidogen; 1-{4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base is amino]-piperidines-1-yl }-ethyl ketone and 1-{4-[6-(4-methane sulfonyl-phenyl amino)-5-nitro-pyrimidine-4-base amino]-piperidines-1-yl }-2,2-dimethyl-third-1-ketone.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022327 number comprises following chemical compound according to formula (III) (being referred to herein as the C4 group): 4-[6-(4-cyano group-2-fluoro-phenyl amino)-5-acetenyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-acetenyl-6-(2-fluoro-4-[1,2,4] triazol-1-yl-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{5-acetenyl-6-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrimidine-4-base is amino }-3-fluoro-benzonitrile; 5-acetenyl-6-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrimidine-4-yl }-(2-fluoro-4-methane sulfonyl-phenyl)-amine; 4-{6-[2,5-two fluoro-4-(2-methane sulfonyl-ethyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(2-sulfamoyl-ethyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2-fluoro-ethyl)-2-methyl-pyridin-3-yl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{2-[4-fluoro-6-(2-isopropoxy-ethyl)-pyridin-3-yl amino]-3-methyl-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2,5-two fluoro-4-(2-[1,2,4] triazol-1-yl-ethyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{5-acetenyl-6-[2-fluoro-4-(4-methoxyl group-pyridine-2-yl)-phenyl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(2-propiono sulfamoyl-ethyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(2-methane sulfonyl-ethyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; And 4-{6-[2,3-two fluoro-4-(2-methane sulfonyl-ethyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022327 number comprises following chemical compound according to formula (III) (being referred to herein as the C5 group): 4-[5-acetyl group-6-(6-methane sulfonyl-pyridin-3-yl amino)-pyrimidine-4-base oxygen base]-piperidines-1-Tetryl formate.; 1-[4-(1-benzyl-azetidine-3-base oxygen base)-6-(6-methane sulfonyl-pyridin-3-yl amino)-pyrimidine-5-yl]-ethyl ketone; 4-[5-cyano group-6-(6-propyl group amino-pyridine-3-base is amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-cyano group-6-(2-fluoro-4-isopropyl amino-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-cyano group-6-(2-fluoro-4-propyl group amino-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-cyano group-6-(2-fluoro-4-propoxyl group-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-cyano group-6-(6-propyl group-pyridin-3-yl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{5-cyano group-6-[4-(2-dimethylamino-ethyl sulfenyl)-2-fluoro-phenyl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{5-cyano group-6-[4-(2-dimethylamino-ethane sulfonyl)-2-fluoro-phenyl amino]-3-oxygen base-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{5-cyano group-6-[2-fluoro-4-(4-methyl-piperazine-1-yl)-phenyl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{5-cyano group-6-[2-fluoro-4-(3-methyl-butyl amino)-phenyl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[5-cyano group-6-(2-fluoro-4-morpholine-4-base-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{5-cyano group-6-[4-(2-dimethylamino-ethylamino)-2-fluoro-phenyl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[5-cyano group-6-(4-dimethylamino-2-fluoro-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{5-cyano group-6-[2-fluoro-4-(2-pyrrolidine-1-base-ethylamino)-phenyl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[6-(2-fluoro-4-methane sulfonyl-phenyl amino)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{5-cyano group-6-[2-fluoro-4-(2-morpholine-4-base-ethylamino)-phenyl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[6-(2-fluoro-4-iodo-phenyl amino)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-cyano group-6-(2-fluoro-4-methane sulfonyl-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(2-fluoro-4-morpholine-4-base-phenyl amino)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(2,5-two fluoro-4-propoxyl group-phenyl aminos)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(2-fluoro-4-propyl group amino-phenyl amino)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(2-methoxyl group-ethylamino)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-(6-{2-fluoro-4-[(tetrahydrochysene-furan-2-ylmethyl)-amino]-phenyl amino }-5-methyl-pyrimidine-4-base oxygen base)-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(2-methane sulfonyl-ethylamino)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-(6-{2-fluoro-4-[(2-methane sulfonyl-ethyl)-methyl-amino]-phenyl amino }-5-methyl-pyrimidine-4-base oxygen base)-piperidines-1-isopropyl formate; 4-[6-(4-bromo-2,5-two fluoro-phenyl aminos)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(4-cyano group-2-fluoro-phenyl amino)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(4-cyano group-2,5-two fluoro-phenyl aminos)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(2,5-two fluoro-4-morpholine-4-base-phenyl aminos)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(6-chloro-2-methyl-pyridin-3-yl amino)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-methyl-6-(2-methyl-6-morpholine-4-base-pyridin-3-yl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-(4,5-dihydro-1H-imidazoles-2-yl)-6-(2-fluoro-4-methane sulfonyl-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; (2-fluoro-4-methane sulfonyl-phenyl)-6-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-5-methyl-pyrimidine-4-yl }-amine; 4-[6-(2-fluoro-4-propoxyl group-phenyl amino)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(2-methane sulfonyl-ethyoxyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(2-methoxyl group-ethyoxyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(2-isopropoxy-ethyoxyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[6-(6-chloro-4-methyl-pyridin-3-yl amino)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(2-fluoro-4-methane sulfonyl-phenyl amino)-5-(N-hydroxy formamidine base)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-amidino-6-(2-fluoro-4-methane sulfonyl-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(tetrahydrochysene-furan-2-ylmethoxy)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[5-methyl-6-(4-methyl-6-morpholine-4-base-pyridin-3-yl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{6-[6-(2-methoxyl group-ethyoxyl)-2-methyl-pyridin-3-yl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2-methoxyl group-ethyoxyl)-4-methyl-pyridin-3-yl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2,5-two fluoro-4-(2-methoxyl group-ethyoxyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(2-isopropoxy-ethyl sulfamoyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2,5-two fluoro-4-(N-hydroxy formamidine base)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[6-(4-carbamoyl-2,5-two fluoro-phenyl aminos)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{6-[(2-fluoro-4-methane sulfonyl-phenyl)-(2-methoxyl group-ethyl)-amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[6-(4-amidino-2,5-two fluoro-phenyl aminos)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{6-[4-(2-ethyoxyl-ethyoxyl)-2-fluoro-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(tetrahydrochysene-pyrans-4-base oxygen base)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(2-hydroxyl-ethyoxyl)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 1-{4-[6-(2-fluoro-4-methane sulfonyl-phenyl amino)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-yl }-Ding-1-ketone; 1-{4-[6-(2-fluoro-4-methane sulfonyl-phenyl amino)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-yl }-penta-1-ketone; 1-{4-[6-(2-fluoro-4-methane sulfonyl-phenyl amino)-5-methyl-pyrimidine-4-base oxygen base]-piperidines-1-yl }-3-methyl-Ding-1-ketone; 4-{6-[2-fluoro-4-(pyridine-2-ylmethoxy)-phenyl amino]-5-methyl-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[2-(2-fluoro-4-methane sulfonyl-phenyl amino)-3-methyl-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-[6-(6-chloro-4-fluoro-pyridin-3-yl amino)-5-cyano group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; With 4-[5-amino-6-(2-fluoro-4-methane sulfonyl-phenyl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022327 number comprises following chemical compound according to formula (III) (being referred to herein as the C6 group): 4-({ [6-(2-fluoro-4-methane sulfonyl-phenyl amino)-5-methyl-pyrimidine-4-yl]-isopropyl-amino }-methyl)-piperidines-1-t-butyl formate.

International Application No. PCT/US2004/022327 disclosed in the No. Specific examples of GPR119 agonists include the Column according to formula (III) compound (referred to herein as Group C7): 4 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -6 - [1 - (3 - Methoxy - propyl) - piperidin-4 - yloxy] -5 - methyl - pyrimidine; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - Pyrimidin-4 - yloxy] - piperidin-1 - yl} -3 - methoxy - propan-2 - ol; 4 - {6 - [2 - fluoro-4 - (5 - methyl-isopropoxy - [1,2,4] oxadiazole Zol-3 - yl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (5 - methoxy - topiramate -2 - yl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [6 - (2 - cyclopropoxyimino Base - ethyl Amino) -2 - methyl - pyridine - 3-yloxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro- -4 - (Pyridin-2 - carbonyl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro - 4 - methane Sulfonyl - phenoxy) -5 - methanesulfonyl-amino - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - methoxy- -6'-methyl-3, 4,5,6 - tetrahydro-2H-[1,2 '] bipyridine-5'-yloxy) -5 - methyl - pyrimidin-4-yloxy] - - piperidine-1 - isobutyl Propyl; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -2 - (4 - trifluoromethyl Methoxy - phenoxy) - propan-1 - one; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy yl] - piperazine -1 - yl} -2 - (4 - (Trifluoromethoxy) - phenoxy) - ethanone; N-(4 - chloro - phenyl) -2 - {4 - [6 - (2 - fluoro - 4 - methanesulfonyl - phenoxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - acetamide; N-(3 - chloro - phenyl) -2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl Yl - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - acetamide; N-(3,5 - dichloro - phenyl) -2 - {4 - [6 - (2 - fluoro- -4 - Methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - acetamide; 2 - {4 - [6 - (2 - fluoro - 4 - methane Sulfonyl - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl}-N-(4 - trifluoromethyl - phenyl) - acetamide; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl}-N-phenyl- - acetamide; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl}-N-(4 - isopropyl - benzene Yl) - acetamide; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - Yl}-N-(4 - methoxy - phenyl) - acetamide; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin - 4 - yloxy Yl] - piperidin-1 - yl}-N-(3 - trifluoromethyl - phenyl) - acetamide; 4 - {6 - [2 - fluoro-4 - (3 - methoxy - propan-1 - sulfonyl) - phenyl Oxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [6 - (2 - isopropoxy - ethyl) -2 - methyl - topiramate -3 - yloxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {5 - methyl-6 - [2 - methyl-6 - (2 - pyridyl -2 - Yl - ethoxy) - pyridin-3 - yloxy] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (thiophen-2 - Carbonyl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - (6 - {6 - [(2 - isopropoxy - B yl) - Methyl - amino] -2 - methyl - pyridine - 3-yloxy} -5 - methyl - pyrimidin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [6 - (2 - isopropoxy - ethane sulfonyl)-2 - methyl - pyridine - 3-yloxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine - 1 - carboxylate isopropyl; 4 - {6 - [6 - (2 - hydroxy - ethane sulfonyl)-2 - methyl - pyridine - 3-yloxy] -5 - methyl - pyrimidin - yloxy Yl} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (6 - amino-2 - methyl - pyridine - 3-yloxy) -5 - methyl - pyrimidin-4-yloxy] - - piperazine -1 - carboxylic acid isopropyl ester; 4 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl-6 - [1 - (3 - methyl - butyl) - piperidin - 4 - yloxy Yl] - pyrimidine; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - morpholine -4 - Yl - ethanone; 1 - (3,4 - dichloro - phenyl) -2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl- - pyrimidin-4 - yloxy Yl] - piperidin-1 - yl} - ethanone; 1 - (3 - chloro - phenyl) -2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - Yloxy] - piperidin-1 - yl} - ethanone; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yl oxy] - Piperidin-1 - yl}-1 - thiophen-3 - yl - ethanone; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin - 4 - yloxy Yl] - piperidin-1 - yl}-1 - phenyl - ethyl ketone; 1 - (2,4 - dimethoxy - phenyl) -2 - {4 - [6 - (2 - fluoro-4 - methane sulfonyl - phenoxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethanone; 4 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl- -6 - [1 - (4 - methyl - pentyl) - piperidin-4 - yloxy] - pyrimidine; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy- ) -5 - methyl - Pyrimidin-4 - yloxy] - piperidin-1 - yl} -3 - isopropoxy - propan-1 - one; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenyl oxy) -5 - Methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -4 - isopropoxy - butan-1 - one; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonamide acyl - phenoxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -3 - hydroxy - propan-1 - one; 2 - {4 - [6 - (2 - fluoro-4 - methane sulfonyl - phenoxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (5 - pyridin-2 - yl - thiophen-2 - yl) - ethanone; 4 - (2 - fluoro-4 - methane sulfonic Acyl - phenoxy) -5 - methyl-6 - [1 - (5 - methyl - hexyl) - piperidin-4 - yloxy] - pyrimidine; 3 - {4 - [6 - (2 - fluoro- -4 - methanesulfonyl Yl - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -3 - oxo - propan-1 - sulfonic acid; 2 - {4 - [6 - ( 2 - fluoro-4 - methane sulfonic Acyl - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl}-1 - thiophen-2 - yl - ethanone; 4 - (2 - fluoro-4 - CH sulfonyl Yl - phenoxy) -5 - methyl-6 - (1 - pentyl - piperidin-4 - yloxy) - pyrimidine; 4 - (1 - butyl - piperidin-4 - yloxy) - 6 - (2 - fluoro-4 - Methanesulfonyl - phenoxy) -5 - methyl - pyrimidine; 4 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin - Yloxy] - piperidin-1 - yl} - cyclohexanecarboxylic acid; 1 - (4 - diethylamino - phenyl) -2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl- - Benzene Oxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethanone; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy yl) -5 - Methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (2 - methyl - 4 - phenyl - furan-3 - yl) - ethanone; 4 - (2 - fluoro - 4 - methanesulfonyl Yl - phenoxy) -6 - (1 - hexyl - piperidin-4 - yloxy) -5 - methyl - pyrimidine; 4 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - butyric acid; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy- ) -5 - methyl- - Pyrimidin-4 - yloxy] - piperidin-1 - yl} - pentan-2 - one; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidine -4 - Yloxy] - piperidin-1 - yl} - hex-2 - one; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl- - pyrimidin-4 - yloxy Yl] - piperidin-1 - yl} - hex-2 - one; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin - yloxy] - piperidine -1 - yl}-4 - methyl - pentan-2 - one; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - Piperidin-1 - yl} -5 - methyl - hex-2 - one; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin - 4 - yloxy] - Piperidin-1 - yl} -6 - methyl - hept-2 - one; 5 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin - 4 - yloxy] - Piperidin-1 - yl}-4 - oxo - pentanoic acid; 5 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yl oxy] - piperidine -1 - yl}-4 - oxo - pentane nitrile; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy yl] - piperidine -1 - Yl} -2 - pyridin-2 - yl - ethanone; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin - yloxy] - Piperidin-1 - yl}-1 - pyridin-4 - yl - ethanone; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin - 4 - yloxy Yl] - piperidin-1 - ylmethyl} - acid; 1 - [1,4] dioxan-2 - yl -2 - {4 - [6 - (2 - fluoro-4 - methanesulfonamide acyl - phenoxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethanone; 1 - (2,3 - dihydro - [1,4] dioxine - 2 - Yl) -2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - acetic ketone; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl}-1 - toluene Base - B Ketone; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (4 - methoxy - Phenyl) - ethanone; 1 - (2 - chloro - phenyl) -2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - Piperidin-1 - yl} - ethanone; 3 - (2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy ] - piperidine-1 - Yl} - acetyl) - benzonitrile; 1 - (2,4 - dimethyl - phenyl) -2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) - 5 - methyl - Pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethanone; 1 - (4 - chloro-3 - methyl - phenyl) -2 - {4 - [6 - (2 - fluoro-4- - methane sulfonyl - phenoxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethanone; 1 - (4 - difluoromethoxy - phenyl) -2 - {4 - [6 - (2 - fluoro-4 - methyl Alkylsulfonyl groups - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethanone; 1 - (2,3 - dihydro - benzo [1,4 ] dioxa Cyclohexyl-6 - yl) -2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin - 1 - yl} - acetic Ketone; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (5 - phenyl - Thiophen-2 - yl) - ethanone; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine -1 - Yl}-1 - thiophen-2 - yl - ethanone; {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4-yloxy] - - piperidin-1 - Yl} - acetate; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - Yl} -3 - methoxy - propan-2 - ol; 4 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -6 - [1 - (4 - methoxy - cyclohexyl) - piperazine -4 - yl Oxy] -5 - methyl - pyrimidine; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine -1 - Yl} - hexan-1 - one; 4 - {6 - [2 - fluoro-4 - (2 - isobutoxy - ethoxy) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy yl} - piperidin-1 - Isopropyl; 4 - {6 - [4 - (2 - cyclopropoxy - ethoxy) -2 - fluoro - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine -1 - Isopropyl; 4 - {6 - [4 - (2 - ethoxy - ethoxy) -2 - fluoro - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine -1 - A Isopropyl; 4 - {6 - [2 - fluoro-4 - (3 - methoxy - propoxy) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine - 1 - carboxylate Isopropyl; 4 - {6 - [2 - fluoro-4 - (2 - pyridin-2 - yl - ethoxy) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine -1 - carboxylic acid Isopropyl; 4 - {6 - [2 - fluoro-4 - (tetrahydro - pyran-4 - yloxy) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine -1 - carboxylic acid Isopropyl; 4 - {6 - [4 - (2 - tert-butoxy - ethoxy) - 2 - fluoro - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine - 1 - carboxylate Isopropyl; 4 - [6 - (2 - fluoro-4 - sulfo - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2,5 - Difluoro-4 - (Trifluoromethoxy) - phenoxy) -5 - ethynyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2,5 - two Fluoro-4 - (Trifluoromethoxy) - phenoxy) -5 - prop-1 - ynyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [5 - ethynyl- -6 - (2 - fluoro-4 - methoxy - phenoxy) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [5 - ethynyl-6 - (6 - methoxy- -4 - Methyl - pyridine - 3-yloxy) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {5 - ethynyl-6 - [6 - (2 - isopropoxy Yl - ethyl) -2 - methyl - pyridine - 3-yloxy] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - cyano - 2 - fluoro - Phenoxy) -5 - ethynyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [5 - ethynyl-6 - (2 - fluoro-4 - [2 , 4] triazol- -4 - Yl - phenoxy) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [5 - ethynyl-6 - (2 - fluoro-4 - [2 , 4] triazol-1 - Yl - phenoxy) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 1 - {4 - [5 - ethynyl-6 - (2 - fluoro-4 - [2 , 4] triazol-1 - Yl - phenoxy) - pyrimidin-4 - yloxy] - piperidin-1 - yl} -3 - pyridin-2 - yl - propan-1 - one; 4 - {5 - ethynyl-6 - [1 - (3 - isopropyl- - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy] - pyrimidin-4 - yloxy} -3 - fluoro - benzonitrile; 5 - ethynyl-4 - (2 - fluoro-4 - Methanesulfonyl - phenoxy) -6 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy] - pyrimidine; 4 - [1 - (3 - Ethyl - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy]-5 - ethynyl-6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy- ) - pyrimidine; 4 - [1 - (3 - ethyl - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy] -6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - Pyrimidine; 4 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl-6 - [1 - (3 - methyl - [1,2,4] oxadiazol-5 - yl ) - piperidin-4 - yl Oxy] - pyrimidine; 4 - [6 - (2 - fluoro-4 - methanesulfonyl-amino - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isobutyl Propyl; cis - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - cyclohexyl} - carbamic acid isobutyl Propyl; Anti - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - cyclohexyl} - carbamic acid isobutyl Propyl; N-{4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - cyclohexyl} -3 - methyl - butyrylcholinesterase Amine; N-{4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - cyclohexyl} - isobutyramide; 4 - {6 - [2,5 - difluoro-4 - (2 - methanesulfonyl - ethyl) - phenoxy] -5 - methyl - pyrimidin-4 - yl oxy} - piperidin-1 - Isopropyl formate Ester; 4 - {6 - [4 - fluoro-6 - (2 - methanesulfonyl - ethyl) - pyridin-3 - yloxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine -1 - A Isopropyl; 4 - {5 - cyclopropyl-6 - [2,5 - difluoro-4 - (2 - hydroxy - ethyl) - phenoxy] - pyrimidin-4 - yloxy} - piperidine -1 - A Isopropyl; 4 - (5 - cyclopropyl-6 - {2,5 - difluoro-4 - [2 - (4 - methoxy - piperidin-1 - yl) - ethyl] - phenoxy yl} - pyrimidin-4 - yl Oxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2,5 - difluoro-4 - (2 - morpholin-4 - yl - ethyl) - phenoxy] -5 - methyl - pyrimidin-4 - Yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - (6 - {2 - fluoro-4 - [2 - (4 - methoxy - piperidin-1 - yl) - ethyl] - benzene oxy} -5 - methyl Yl - pyrimidin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [6 - (2 - fluoro - ethyl) -2 - methyl - pyridine - 3-yloxy ] -5 - methyl Yl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (1 - hydroxy - methyl-cyclopropyl) - phenoxy] - 5 - A Yl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {2 - [2,5 - difluoro-4 - (2 - methanesulfonyl - ethyl) - phenoxy Yl] -3 - methyl - pyridin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; (R) -4 - (6 - {2 - fluoro-4 - [2 - (3 - methyl oxy - piperidin - Yl) - ethyl] - phenoxy} -5 - methyl - pyrimidin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; (S) -4 - (6 - {2 - fluoro - 4 - [2 - (3 - methyl Oxy - piperidin-1 - yl) - ethyl] - phenoxy} -5 - methyl - pyrimidin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; (R) -4 - (5 - B Alkynyl -6 - {2 - fluoro-4 - [2 - (2 - methoxy - piperidin-1 - yl) - ethyl] - phenoxy} - pyrimidin-4 - yloxy) - piperidine - 1 - carboxylate isopropyl Esters; (S) -4 - (2 - {2 - fluoro-4 - [2 - (2 - methoxy - piperidin-1 - yl) - ethyl] - phenoxy}-3 - methyl - pyridin-4 - yloxy) - piperidine - 1 - carboxylate isopropyl; 4 - {6 - [4 - fluoro-6 - (2 - morpholin-4 - yl - ethyl) - pyridin-3 - yloxy] -5 - methyl - pyrimidin - 4 - yl oxy} - Piperidine-1 - carboxylic acid isopropyl ester; 4 - {5 - ethynyl-6 - [4 - fluoro-6 - (2 - methanesulfonyl - ethyl) - pyridin-3 - yloxy] - pyrimidin-4 - Yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {2 - [2,5 - difluoro-4 - (2 - isopropoxy - ethyl) - phenoxy] -3 - methyl Base - pyridine -4 - Yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (2 - propionyl-sulfamoyl - ethyl) - phenoxy] -5 - methyl - Pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (2 - sulfamoyl - ethyl) - phenoxy] -5 - methyl Base - ethyl -4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2,5 - difluoro-4 - (2 - sulfamoyl - ethyl) - phenoxy] - 5 - ethynyl- - Pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2,5 - difluoro-4 - (2 - [1,2,4] triazol-1 - Base - ethyl) - phenoxy Yl] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2,3 - difluoro-4 - (2 - methanesulfonyl - B yl) - Phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - (2 - {2 - fluoro-4 - [2 - (6 - methoxy- - pyridin-2 - Yl) - ethyl] - phenoxy}-3 - methyl - pyridin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - (6 - {2 - fluoro-4 - [2 - (3 - methoxy- - Pyridin-2 - yl) - ethyl] - phenoxy} -5 - methyl - pyrimidin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (3 - fluoro- -1 - group - Pyridin-4 - yloxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (5'-methoxy-6 - methyl yl - [2,2 '] United pyridin-5 - yloxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {5 - ethynyl-6 - [2 - fluoro-4- - (4 - Methoxy - pyridin-2 - yl) - phenoxy] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (3 - methoxy - Pyridin-2 - yl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - (6 - {2,5 - difluoro-4 - [2 - (3 - Methoxy - piperidin-1 - yl) - ethyl] - phenoxy} -5 - methyl - pyrimidin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; and 4 - (6 - {2,5 - difluoro-4 - [2 - (3 - methoxy - piperidin-1 - yl) - ethyl] - phenoxy} -5 - ethynyl - pyrimidin-4 - yloxy) - piperidine - 1 - carboxylate isopropyl. ...

International Application No. PCT/US2004/022327 disclosed in the No. Specific examples of GPR119 agonists include the Column according to formula (III) compound (referred to herein as Group C8): 4 - [6 - (2 - fluoro-4 - morpholin-4 - yl - phenoxy) -5 - methyl Yl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidine -4 - Yloxy] - piperidin-1 - yl} - [6 - (2 - pyrrolidin-1 - yl - ethyl) - pyridin-3 - yl] - methanone; (6 - amino - pyridine - 3 - Yl) - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; 4 - [5 - B -6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro - phenyl oxygen Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [6 - (2 - isopropoxy - ethyl amino) -2 - methyl - Pyridin-3 - yloxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [6 - (2 - hydroxy - ethyl sulfide Yl) -2 - methyl - pyridine - 3-yloxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [5 - methyl-6 - (2 - Methyl-6 - pentyl - pyridin-3 - yloxy) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 2 - {4 - [6 - (2 - fluoro-4- - methane sulfonic Acyl - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (3 - fluoro - phenyl) - ethanone; 4 - (2 - fluoro - 4 - methanesulfonyl Yl - phenoxy) -5 - methyl-6 - [1 - (2 - pyridin-3 - yl - ethyl) - piperidin-4 - yloxy] - pyrimidine; 2 - {4 - [6 - (2 - fluoro-4 - methane sulfonic Acyl - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (4 - (Trifluoromethoxy) - phenyl) - ethanone; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl}-1 - pyridin - 2 - group - B Ketone; 4 - {6 - [6 - (2 - methoxy - ethane sulfonyl) -2 - methyl - pyridine - 3-yloxy] -5 - methyl - pyrimidin-4 - yl oxy} - piperidine - 1 - carboxylate isopropyl; 4 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -6 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidine -4 - Yloxy] -5 - methyl - pyrimidine; 4 - (6 - {2 - fluoro-4 - [(2 - hydroxy - ethyl-carbamoyl) - methyl] - phenoxy}-5 - methyl - Pyrimidin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (5 - iodo - pyridin-2 - yloxy) -5 - methyl - pyrimidin-4 - yloxy ] - Piperidine-1 - carboxylic acid isopropyl ester; 4 - (6 - {2 - Fluoro -4 - [N-(2 - isopropoxy - ethyl) - carbamimidoyl] - phenoxy} -5 - methyl Base - pyrimidin-4 - Yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - carboxy-2 - fluoro - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine -1 - Isopropyl; 4 - (4 - bromo - 2 - fluoro - phenoxy) -6 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperazine -4 - yl oxy] -5 - Methyl - pyrimidine; 4 - [6 - (5 - methanesulfonyl-- pyridin-2 - yloxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl Ester; 4 - {6 - [6 - (2 - hydroxy - ethyl-amino) -2 - methyl - pyridine - 3-yloxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine -1 - A Isopropyl; 4 - [5 - cyclopropyl-6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl Ester; 4 - {6 - [6 - (2 - methanesulfonyl-- ethyl amino) -2 - methyl - pyridine - 3-yloxy] -5 - methyl - pyrimidin-4 - yloxy} - piperazine -1 - carboxylic acid isopropyl ester; 4 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin - 1 - Yl} -4 - oxo - butyric acid; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine -1 - Yl} -1 - (3 - (trifluoromethyl) - phenyl) - ethanone; 4 - {6 - [6 - (2 - methoxy - ethylthio) - 2 - methyl - pyridine - 3 - yloxy] -5 - Methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 1 - (2,5 - dimethoxy - phenyl) -2 - {4 - [6 - (2 - fluoro- -4 - methane sulfonic Acyl - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethanone; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl- - phenoxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl}-1 - pyridin-2 - yl - ethanone; 4 - [6 - (6 - chloro-2 - methyl- - pyridin-3 - yl oxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - Methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (4 - fluoro - phenyl) - ethanone; 2 - {4 - [6 - (2 - fluoro-4 - CH sulfonyl - phenoxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (4 - (trifluoromethyl) - phenyl) - ethanone; 1 - {4 - [6 - (2 - fluoro-4 - methane Sulfonyl - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -3,3 - dimethyl - butan-2 - one; 2 - {4 - [ 6 - (2 - fluoro-4 - Methanesulfonyl - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl}-1 - pyridin-3 - yl - ethanone; 1 - {4 - [6 - (2 - fluoro- -4 - Methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - butan-2 - one; 4 - (6 - {2 - fluoro - 4 - [(2 - iso Propoxy - ethylcarbamoyl) - methyl] - phenoxy} -5 - methyl - pyrimidin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (4 - methane sulfonyl - Phenyl) - ethanone; 1 - (4 - chloro - phenyl) -2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin - 4 - yloxy] - Piperidin-1 - yl} - ethanone; 4 - (2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy ] - piperidine-1 - Yl} - acetyl) - benzonitrile; 1 - (3,4 - difluoro - phenyl) -2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidine -4 - Yloxy] - piperidin-1 - yl} - ethanone; 4 - {6 - [2 - fluoro-4 - (2 - isopropoxy - carbamoyl-ethyl) - phenoxy] -5 - methyl - Pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidine -4 - Yloxy] - piperidin-1 - yl} - butan-1 - one; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl- - pyrimidin-4 - yloxy Yl] - piperidin-1 - yl} - pentan-1 - one; 4 - [6 - (2,4 - difluoro - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine -1 - carboxylic acid isopropyl Ester; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -3 - methyl - butan - One; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -4 - methyl - pent-1 - One; 1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -5 - methyl - hex-1 - Ketone; 4 - {6 - [2 - fluoro-4 - (2 - methoxy - ethylcarbamoyl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine - 1 - A Isopropyl; 4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - bromo - 2 - fluoro - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (methoxy- Yl - methyl - carbamoyl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 1 - {4 - [6 - (2 - fluorine -4 - Methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -3 - methoxy - propan-1 - one; 4 - [6 - (4 - Cyanide -2 - fluoro - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [5 - (5 - amino-4 ,5 - dihydro - Oxazol-2 - yl) -6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [6 - (2 - methoxy - ethyl amino) -2 - methyl - pyridine - 3-yloxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine -1 - A Isopropyl; 4 - {6 - [6 - (3 - methanesulfonyl-- pyrrolidin-1 - yl) - 2 - methyl - pyridine - 3-yloxy] -5 - methyl - pyrimidin-4 - Yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (6 - benzyl-amino-2 - methyl - pyridine - 3-yloxy) -5 - methyl - pyrimidin - base Oxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - carbamoyl-2 - fluoro - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine pyridine - 1 - carboxylate isopropyl; 4 - {6 - [2 - fluoro-4 - (2 - isopropoxy - ethylamino) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy } - piperazine -1 - carboxylic acid isopropyl ester; 4 - (6 - {2 - fluoro-4 - [(tetrahydro - furan-2 - ylmethyl) - amino] - phenoxy} -5 - methyl - pyrimidin - 4 - Base Oxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - (6 - {6 - [(2 - methanesulfonyl - ethyl) - methyl - amino] -2 - methyl - pyridine - 3 - yl oxygen Yl} -5 - methyl - pyrimidin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro-4 - hydroxy-carbamoyl - phenoxy) -5 - Methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (2 - pyrrolidin-1 - yl - ethylcarbamoyl) - Phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (4 - isopropyl - piperazine -1 - carbonyl Yl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (2 - morpholino - 4 - yl - B Yl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (2 - methanesulfonyl- - B Yl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2 - fluoro-4 - (2 - hydroxy - ethyl yl) - benzene Oxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - carboxy-2 - fluoro - phenoxy) -5 - methyl - Pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - dimethyl-carbamoyl-2 - fluoro - phenoxy) -5 - methyl Yl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro-4 - sulfamoyl - phenoxy) -5 - methyl - pyrimidin-4 - Yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro-4 - propionyl-sulfamoyl - phenoxy) -5 - methyl - pyrimidin-4 - yloxy Yl] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [5 - ethynyl-6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) - pyrimidin-4 - yloxy] - piperidine - 1 - carboxylate isopropyl; 4 - {6 - [2 - fluoro-4 - (2 - phosphono group - ethyl) - phenoxy] -5 - methyl - pyrimidin-4 - yl oxy} - piperidin-1 - Isopropyl; 4 - [5 - bromo-6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - (6 - {2 - fluoro-4 - [2 - (2 - methanesulfonyl-- pyrrolidin-1 - yl) - 2 - oxo - ethyl] - phenoxy} -5 - methyl - pyrimidine -4 - yloxy Yl) - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - carbamoyl-2 - fluoro - phenoxy) -5 - methyl - pyrimidin-4-yloxy] - - Piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro-4 - {[(tetrahydro - furan-2 - ylmethyl) - carbamoyl] - methyl} - phenoxy) -5 - Methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro-3 - sulfamoyl - phenoxy) -5 - methyl - pyrimidin - 4 - Yloxy] - piperidine-1 - carboxylic acid isopropyl ester; C-{4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy Yl] - piperidin-1 - yl}-C-(4 - fluoro - phenyl) - methylene - amine; 3 - tert-butoxy-1 - {4 - [6 - (2 - fluoro-4 - CH sulfonyl - phenoxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - propan-1 - one China; - ethoxy-1 - {4 - [6 - (2 - fluoro - 4 - methanesulfonyl - Phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethanone; {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy- ) -5 - Methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} - (tetrahydro - furan-2 - yl) - methanone; (S) -1 - {4 - [6 - (2 - fluoro- -4 - methane sulfonyl - Phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -3 - methyl - 2 - methylamino - butan-1 - one; 4 - (6 - { 2 - fluoro- -4 - [2 - (3 - hydroxy - piperidin-1 - yl) - 2 - oxo - ethyl] - phenoxy} -5 - methyl - pyrimidin-4 - yloxy) - piperidine - 1 - carboxylic acid isopropyl Ester; 4 - {6 - [2 - fluoro-4 - (2 - morpholin-4 --2 - oxo - ethyl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy } - piperidine-1 - carboxylic acid Isopropyl; 4 - {6 - [2 - fluoro-4 - (2 - imidazol-1 - yl - ethyl) - phenoxy] -5 - methyl - pyrimidin-4 - yloxy} - piperidine - 1 - carboxylate iso Propyl; 4 - {6 - [2 - fluoro-4 - (2 - [1,2,3] triazol-1 - yl - ethyl) - phenoxy] -5 - methyl - pyrimidin - yloxy} - piperidine-1 - A Isopropyl; (R) -1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin - 1 - yl} -3 - Methyl-2 - methylamino - butan-1 - one; (S) -1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - Piperidin-1 - yl} -3 - hydroxy - butan-1 - one; (R)-N-(1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - Yloxy] - piperidine-1 - carbonyl}-2 - methyl - propyl) - acetamide; (S)-N-(1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl- - phenoxy Yl) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carbonyl}-2 - methyl - propyl) - acetamide; (R)-N-(2 - {4 - [ 6 - (2 - fluoro-4 - Methanesulfonyl - phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - methyl - 2 - oxo - ethyl) - acetamide; (S)-N-(2 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - yl} -1 - methyl -2 - Oxo - ethyl) - acetamide; 4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - armor Acid (S) - tetrahydro - furan-3 - yl ester; 4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4-yloxy] - - piperidine - 1 - carboxylate (R) - tetrahydro - furan-3 - yl ester; 4 - [6 - (2 - amino -4 - ethanesulfonyl - phenoxy) -5 - methyl - pyrimidin-4 - yl oxygen Yl] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid Isopropyl; (1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carbonyl} -2 - A Yl - propyl) - carbamic acid tert-butyl ester; 4 - {6 - [2 - fluoro-4 - (6 - methoxy - pyridine - 3 - yl) - phenoxy] -5 - methyl - pyrimidin - 4 - Base Oxy} - piperidine-1 - carboxylic acid isopropyl ester; 3 - amino-1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy) -5 - methyl - pyrimidin-4 - Yloxy] - piperidin-1 - yl}-4 - methyl - pentan-1 - one China; - Amino-1 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenoxy- ) -5 - methyl - Pyrimidin-4 - yloxy] - piperidin-1 - yl} -3 - methyl - butan-1 - one; 4 - {6 - [2 - fluoro-4 - (2 - isopropoxy - ethoxyethyl yl) - phenoxy Yl] -5 - methyl - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; and 4 - [5 - methyl-6 - (4 - sulfo - phenoxy) - pyrimidine -4 - Yloxy] - piperidine-1 - carboxylic acid isopropyl ester. ...

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022327 number comprises following chemical compound according to formula (III) (being referred to herein as the C9 group): 4-({ cyclopropyl-[6-(2-fluoro-4-methane sulfonyl-phenoxy group)-5-methyl-pyrimidine-4-yl]-amino }-methyl)-piperidines-1-t-butyl formate; 4-({ cyclopropyl-[6-(2-fluoro-4-methane sulfonyl-phenoxy group)-5-methyl-pyrimidine-4-yl]-amino }-methyl)-piperidines-1-isopropyl formate; 4-({ [6-(2-fluoro-4-methane sulfonyl-phenoxy group)-5-methyl-pyrimidine-4-yl]-isopropyl-amino }-methyl)-piperidines-1-isopropyl formate; And 4-({ cyclopropyl methyl-[6-(2-fluoro-4-methane sulfonyl-phenoxy group)-5-methyl-pyrimidine-4-yl]-amino }-methyl)-piperidines-1-isopropyl formate.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022327 number comprises following chemical compound according to formula (III) (being referred to herein as the C10 group): 4-[6-(2-fluoro-4-methane sulfonyl-phenyl amino)-5-methyl-pyrimidine-4-base sulfenyl]-piperidines-1-isopropyl formate.

The case description of GPR119 agonist in international application case PCT/US2004/022417 number (open) with WO05/007658, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/US2004/022417 number is formula (IV) chemical compound:

Wherein:

D is O, S, S (O), S (O) ₂, CR ₁R ₂Or N-R ₂, R wherein ₁Be selected from by H, C _1-8Alkyl, C _1-4The group that alkoxyl, halogen and hydroxyl are formed;

E is N, C or CR ₃, R wherein ₃Be H or C _1-8Alkyl;

When E is N or CR ₃The time,

Be singly-bound, or when E is C,

Be two keys;

K is C _3-6Cycloalkylidene or C _1-3Alkylidene, wherein each group replaces through 1 to 4 substituent group according to circumstances, and described substituent group is selected from by C _1-3Alkyl, C _1-4Alkoxyl, carboxyl, cyano group, C _1-3The group that alkylhalide group and halogen are formed; Or K is a key;

Q is NR ₄, O, S, S (O) or S (O) ₂, R wherein ₄Be H or C _1-8Alkyl, and described C _1-8Alkyl is according to circumstances through C _2-8Dialkylamine replaces;

T is N or CR ₅

M is N or CR ₆

J is N or CR ₇

U is C or N;

V is N, CR ₈, or V is a key;

W is N or C;

X is O, S, N, CR ₉Or NR ₁₁

Y is O, S, N, CR ₁₀Or NR ₁₂

Z is C or N;

R ₅, R ₆, R ₇, R ₈, R ₉And R ₁₀Be selected from independently of one another by H, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, amino, C _1-4Alkyl amino, C _2-8Dialkyl amido, Methanamide, cyano group, C _3-6Cycloalkyl, C _2-6Dialkylformamide, C _2-6Dialkyl group sulfonamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, hydroxyl, hydroxyl amino and nitro are formed; Wherein said C _2-6Thiazolinyl, C _1-8Alkyl, C _2-6Alkynyl and C _3-6Cycloalkyl replaces through 1,2,3 or 4 substituent group separately according to circumstances, and described substituent group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _1-4Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Alkyl sulfide urea groups, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group, C _1-4The group that alkylhalide group sulfenyl, halogen, hydroxyl, hydroxyl amino and nitro are formed;

R ₁₁And R ₁₂Be selected from by C independently of one another _2-6Thiazolinyl, C _1-8Alkyl, C _2-6Alkynyl or C _3-6The group that cycloalkyl is formed, described group replaces through 1,2,3 or 4 substituent group separately according to circumstances, and described substituent group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _1-4Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Alkyl sulfide urea groups, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group, C _1-4The group that alkylhalide group sulfenyl, halogen, hydroxyl, hydroxyl amino and nitro are formed;

Ar ₁Be separately according to circumstances through R ₁₃, R ₁₄, R ₁₅, R ₁₆And R ₁₇The aryl or the heteroaryl that replace; R wherein ₁₃Be selected from by C _1-5Acyl group, C _1-6Acyl group sulfonamide, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl amino, C _1-6Alkyl formamides, C _1-4Alkylthio Methanamide, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, aryl sulfonyl, amidino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _3-7Cycloalkyl oxy, C _2-6Dialkyl amido, C _2-6Dialkylformamide, C _2-6Dialkyl group thioformamide, guanidine radicals, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group sulfenyl, heterocyclic radical, heterocyclic radical-oxygen base, heterocyclic radical sulfonyl, heterocyclic radical-carbonyl, heteroaryl, heteroaryl carbonyl, hydroxyl, nitro, C _4-7The group that oxo-cycloalkyl, phenoxy group, phenyl, sulfonamide, sulfonic acid and mercaptan are formed, and wherein said C _1-5Acyl group, C _1-6Acyl group sulfonamide, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl amino, C _1-6Alkyl sulfonamide, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, aryl sulfonyl, amidino, C _2-6Dialkyl amido, heterocyclic radical, heterocyclic radical-carbonyl, heteroaryl, phenoxy group and phenyl replace through 1 to 5 substituent group according to circumstances, and described substituent group is independently selected from by C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-7Alkyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _3-7Cycloalkyl oxy, C _2-6Dialkyl amido, C _2-6Dialkylformamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group sulfenyl, heteroaryl, heterocyclic radical, hydroxyl, nitro, phenyl and phosphonato, and wherein said C _1-7Alkyl and C _1-4Alkyl formamides replaces through 1 to 5 substituent group separately according to circumstances, and described substituent group is selected from by C _1-4The group that alkoxyl and hydroxyl are formed; Or

R ₁₃Be the group of formula (IVA):

(IVA)

Wherein:

" p " and " r " is 0,1,2 or 3 independently; And

R ₁₈Be H, C _1-5Acyl group, C _2-6Thiazolinyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _2-6Dialkylformamide, halogen, heteroaryl or phenyl, and wherein said heteroaryl or phenyl replace through 1 to 5 substituent group according to circumstances, and described substituent group is independently selected from by C _1-4Alkoxyl, amino, C _1-4Alkyl amino, C _2-6Alkynyl, C _2-8Dialkyl amido, halogen, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group and hydroxyl are formed;

R ₁₄, R ₁₅, R ₁₆And R ₁₇Be selected from independently of one another by H, C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _2-6Alkynyl, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl urea groups, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _2-6Dialkylformamide, halogen, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4The group that alkylhalide group sulfenyl, hydroxyl and nitro are formed; Or

Two adjacent R ₁₄, R ₁₅, R ₁₆And R ₁₇Form and Ar with the atom that it connected ₁Condensed 5 yuan, 6 yuan or 7 yuan of cycloalkyl, cycloalkenyl group or heterocyclic radicals, wherein said 5 yuan, 6 yuan or 7 yuan of groups replace through halogen according to circumstances; And

R ₂Be selected from by C _1-8Alkyl, C _2-6Alkynyl, amino, aryl, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group, halogen, heteroaryl and hydroxyl are formed; And wherein said C _1-8Alkyl, aryl and heteroaryl replace through 1 to 5 substituent group separately according to circumstances, and described substituent group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _3-6Cycloalkyl-C _1-3Inferior assorted alkyl, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _2-6Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Alkyl sulfide urea groups, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group, C _1-4The group that alkylhalide group sulfenyl, halogen, heterocyclic radical, hydroxyl, hydroxyl amino and nitro are formed; Or

R ₂Be-Ar ₂-Ar ₃, Ar wherein ₂And Ar ₃Be aryl or the heteroaryl that replaces through 1 to 5 substituent group according to circumstances separately independently of one another, described substituent group is selected from by H, C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, amino, C _1-4Alkyl amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _1-4Halogen alkoxyl, C _1-4The group that alkylhalide group, halogen, hydroxyl and nitro are formed; Or

R ₂Be the group of formula (IVB):

Wherein:

R ₁₉Be H, C _1-8Alkyl, C _3-7Cycloalkyl, aryl, heteroaryl or OR ₂₁And R ₂₀Be F, Cl, Br, CN or NR ₂₂R ₂₃R wherein ₂₁Be H, C _1-8Alkyl or C _3-7Cycloalkyl, and R ₂₂And R ₂₃Be H, C independently _1-8Alkyl, C _3-7Cycloalkyl, aryl or heteroaryl;

Or

R ₂Be the group of formula (IVC):

Wherein:

I) when D be CR ₂R ₃The time, G is-C (O)-,-C (O) NR ₂₅-,-NR ₂₅C (O)-,-NR ₂₅-,-NR ₂₅C (O) O-,-OC (O) NR ₂₅-,-CR ₂₅R ₂₆NR ₂₇C (O)-,-CR ₂₅R ₂₆C (O) NR ₂₇-,-C (O) O-,-OC (O)-,-C (S)-,-C (S) NR ₂₅-,-C (S) O-,-OC (S)-,-CR ₂₅R ₂₆-,-O-,-S-,-S (O)-,-S (O) ₂-or key; Or

Ii) working as D is NR ₂The time, G is-CR ₂₅R ₂₆C (O)-,-C (O)-,-CR ₂₅R ₂₆C (O) NR ₂₇-,-C (O) NR ₂₅-,-C (O) O-,-C (S)-,-C (S) NR ₂₅-,-C (S) O-,-CR ₂₅R ₂₆-,-S (O) ₂-or key;

R wherein ₂₅, R ₂₆And R ₂₇Be H or C independently of one another _1-8Alkyl; And R ₂₄Be H, C _1-8Alkyl, C _3-7Cycloalkyl, phenyl, heteroaryl or heterocyclic radical, each group replace through 1 to 5 substituent group according to circumstances, and described substituent group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _2-6Thiazolinyl, C _1-4Alkoxyl, C _1-7Alkyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _2-6Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Alkyl sulfide urea groups, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group, C _1-4The group that alkylhalide group sulfenyl, halogen, heteroaryl, heterocyclic radical, hydroxyl, hydroxyl amino, nitro, phenyl, phenoxy group and sulfonic acid are formed, wherein said C _1-4Alkoxyl, C _1-7Alkyl, C _1-4Alkyl amino, heteroaryl, phenyl and phenoxy group replace through 1 to 5 substituent group separately according to circumstances, and described substituent group is selected from by C _1-5Acyl group, C _1-5Acyloxy, C _1-4Alkoxyl, C _1-8Alkyl, C _1-4Alkyl amino, C _1-4Alkyl formamides, C _1-4Alkylthio Methanamide, C _1-4Alkyl sulfonamide, C _1-4Alkyl sulphinyl, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, C _1-4Alkyl sulfide urea groups, C _1-4Alkyl urea groups, amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-7Cycloalkyl, C _2-8Dialkyl amido, C _2-6Dialkylformamide, C _2-6Dialkyl group thioformamide, C _2-6Dialkyl group sulfonamide, C _1-4Alkyl sulfide urea groups, C _1-4Halogen alkoxyl, C _1-4Alkylhalide group, C _1-4Alkylhalide group sulfinyl, C _1-4Alkylhalide group sulfonyl, C _1-4Alkylhalide group, C _1-4The group that alkylhalide group sulfenyl, halogen, heterocyclic radical, hydroxyl, hydroxyl amino, nitro and phenyl are formed;

Condition is that Z and U not all are N.

International Application No. PCT/US2004/022417 disclosed in the No. Specific examples of GPR119 agonists include the Column according to formula (IV) compound (referred to herein as Group D1): 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [1 - (4 - methanesulfonyl - phenyl) -3 - methyl-1H-pyrazol azole and [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [1 - (4 - methanesulfonyl - phenyl) -3,6 - dimethyl - 1H-pyrazole Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isobutyl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3, 4-d] Pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 1 - (4 - methanesulfonyl - phenyl) -4 - (piperidin-4 - yloxy)-1H-pyrazole And [3,4-d] pyrimidine; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine -1 - yl} - Pyridin-3 - yl - methanone; (3 - fluoro - phenyl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy Yl] - piperidin-1 - yl} - methanone; (1 - t-butyl-5 - methyl-1H-pyrazol-4 - yl) - {4 - [1 - (4 - methanesulfonyl - benzene yl)-1H- Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; (5 - tert-butyl-2 - methyl-2H-pyrazol-3 - Yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methyl ketone; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [1 - (4 - Methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (4 - methanesulfonamide Acyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - piperidine-1 - carboxylic acid isobutyl ester; furan-2 - yl - {4 - [1 - (4 - A Alkylsulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; {4 - [1 - (4 - CH sulfonyl - Phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - (1 - methyl-1H-pyrrol-2 - yl) - methyl ketone; 2 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - pyridine-3 - yl - Ethanone; 2 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - pyridine -2 - Yl - ethanone; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin- - yl} - (5 - Methyl - pyridin-3 - yl) - methanone; (4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4-yloxy] - - piperidine -1 - Yl} - (2 - methyl - pyridine - 3 - yl) - methanone; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d ] pyrimidin-4 - yl Oxy] - piperidin-1 - yl} - (6 - methyl - pyridine - 3 - yl) - methanone; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] Pyrimidin-4 - yloxy] - piperidin-1 - yl} - (5 - methyl - isoxazol-3 - yl) - methanone; 2 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H- Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl}-1 - thiophen-2 - yl - ethanone; 4 - (1 - benzyl - azetidin - ³ - Oxygen Yl) -1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine; 3 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazole and [3,4-d] pyrimidin-4 - ylamino] - piperidine-1 - carboxylic acid tert-butyl ester; 1 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [ 3,4-d] Pyrimidin-4 - yloxy] - piperidin-1 - yl} -3,3 - dimethyl - butan-2 - one; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H- pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - pyrazine-2 - yl - methanone; {4 - [1 - (4 - methanesulfonyl - phenyl) -1H-pyrazole And [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - (5 - methyl - pyrazine-2 - yl) - methanone; {4 - [1 - (4 - methane sulfonyl - benzene Yl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - pyrimidin-5 - yl - methanone; {4 - [1 - (4 - methane sulfonyl - Phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - pyridazin-4 - yl - methanone; {4 - [1 - ( 4 - methane sulfonyl - Phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - thiophene-2 - yl - methanone; (3,4 - dimethoxyphenyl Base - isoxazole -5 - Yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl } - methanone; 3 - Tert-butoxy-1 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - yl} - C -1 - One; (3 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin- - yl} -3 - oxo- - Propyl) - methyl - carbamic acid tert-butyl ester; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy Yl] - piperidin-1 - yl} - (6 - (trifluoromethyl) - pyridin-3 - yl) - methanone; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazole and [3,4-d] pyrimidin-4 - ylamino] - cyclohexyl} - carbamic acid tert-butyl ester; N-[1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - cyclohexane-1 ,4 - diamine; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3, 4-d] pyrimidin-4 - Yloxy] - piperidin-1 - yl} - (4 - methyl - [1,2,3] thiadiazol-5 - yl) - methanone; (3,5 - dimethyl - isoxazole -4 - Yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methyl ketone; (2,5 - Dimethyl-2H-pyrazol-3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy ] - piperidine -1 - Yl} - methanone; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin - 1 - yl} - (3 - Methyl - isoxazol-5 - yl) - methanone; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy ] - piperazine -1 - thio-carbonate-4 - yl amide; N-{4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl Amino] - cyclohexyl} - nicotinamide; 3 - tert-butoxy-N-{4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine -4 - Yl amino] - cyclohexyl} - propionamide; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl amino Yl] - cyclohexyl} - carbamic acid tert-butyl ester; (3,5 - dimethyl - isoxazol-4 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H- Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; 4 - [1 - (3,5 - bis - (trifluoromethyl) - phenyl) -1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 3 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3, 4-d] Pyrimidin-4-yloxy] - - azetidin-1 - carboxylic acid isopropyl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine -4 - Yloxy] - piperidine-1 - carboxylic acid butyl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl oxygen Yl] - piperidine-1 - carboxylic acid ester; 4 - [1 - (3 - fluoro - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin - 1 - tert- Butyl; 4 - [1 - (2,4 - difluoro - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester ; {4 - [1 - (2,4 - difluoro - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - cyclohexyl} - carbamic acid tert-butyl ester; {4 - [1 - (3 - fluoro - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - cyclohexyl} - carbamic acid tert-butyl ester; N-[1 - (4 - Methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - cyclohexane-1 ,4 - diamine; {3 - [1 - (4 - methanesulfonyl- - Phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - piperidin-1 - yl} - (6 - methyl - pyridine - 3 - yl) - methanone; {3 - [1 - (4 - methyl Alkylsulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - piperidin-1 - yl} - (2 - methyl - pyridine - 3 - yl) - methyl ketone; {3 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - piperidin-1 - yl} - (5 - methyl- - pyridine-3 - Yl) - methanone; {3 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - piperidin-1 - yl} - pyridine -3 - Yl - methanone; {3 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - piperidin - yl} - (1 - Methyl-1H-pyrrol-3 - yl) - methanone; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy yl] - Cyclohexyl} - carbamic acid tert-butyl ester; N-[1 - (2,4 - difluoro - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - cyclohexane - 1,4 - Diamine; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - ( 4 - trifluoromethanesulfonic Yl - pyridin-3 - yl) - methanone; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine -1 - Cyclohexyl carboxylic acid; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - acid tetramethyl H - pyran-4 - yl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin - 1 - carboxylic acid Cyclopentyl; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tetrahydro - furosemide Furans -3 - yl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tetrahydro - Furan-3 - yl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid four Hydrogen - thio-pyran-4 - yl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine -1 - Ring acid ester; (6 - tert-butyl-- pyridin-3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine - 4 - Yloxy] - piperidin-1 - yl} - methanone; (4 - {[1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - Methyl} - cyclohexyl) - carbamic acid tert-butyl ester; N-{4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - Ylamino] - cyclohexylmethyl} - nicotinamide; N-{4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl Amino] - cyclohexylmethyl} -6 - methyl - nicotinamide; 4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidine -4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine -4 - Yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - {[1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4 - d] Pyrimidin-4 - ylamino] - methyl} - piperidine-1 - carboxylic acid tert-butyl ester; 3 - {[1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d ] Pyrimidin-4 - ylamino] - methyl} - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({ethyl - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - {1 - [2 - (2 - dimethylamino - ethoxy ) -4 - methyl Alkylsulfonyl - phenyl]-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid tert-butyl ester; 3 - [1 - (2 - fluoro-4- - Methane Sulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [1 - (4 - methanesulfonyl - Phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid pyridin-3 - yl ester acid tert-butyl ester; 4 - [1 - (4 - A Alkylsulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - acid 2 - pyridin-3 - yl - ester; 4 - [1 - (4 - Methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - acid 3 - pyridin-3 - yl - propyl; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - acid 2 - dimethylamino - Ethyl; 4 - {[1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - methyl - amino} - piperidin-1 - carboxylate Butyl; 4 - [1 - (2,4 - difluoro - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester ; 4 - ({B Yl - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - amino} - methyl) - piperidine - Formic acid Propyl; 4 - ({ethyl - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - amino} - methyl) - Piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - dimethylamino-1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - Yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 1 - (4 - {[1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - Methyl - amino} - piperidin-1 - yl) -3,3 - dimethyl - butan-2 - one; 4 - {[1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] Pyrimidin-4 - yl] - methyl - amino} - piperidine-1 - carboxylic acid butyl ring; and 4 - [({1 - [4 - (2 - methanesulfonyl - ethyl) - phenyl]-1H - Pyrazolo [3,4-d] pyrimidin-4 - yl} - methyl - amino) - methyl] - piperidine-1 - carboxylic acid tert-butyl ester. ...

International Application No. PCT/US2004/022417 disclosed in the No. Specific examples of GPR119 agonists include the Column according to formula (IV) compound (referred to herein as Group D2): 4 - ({[1 - (2,5 - difluoro - phenyl)-1H-pyrazolo [3,4-d] Pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 2 - {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl) - 1H- Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (4 - (Trifluoromethoxy) - phenyl) - ethanone; 2 - {4 - [1 - (2 - fluoro-4 - Methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (3 - fluoro - phenyl) - ethanone ; 2 - {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl } -1 - pyridine -2 - Yl - ethanone; (2,5 - dimethyl - furan-3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4 -d] pyrimidin-4 - Yloxy] - piperidin-1 - yl} - methanone; 4 - ({(2 - dimethylamino - ethyl) - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazole and [3,4-d] pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({(2 - dimethylamino - ethyl) - [1 - (2 - fluoro-4 - Methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [1 - ( 2 - Dimethyl-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - {ethyl - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - amino} - ethyl) - piperazine triazine-1 - A Acid tert-butyl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl thio] - piperidine-1 - carboxylic acid tert-butyl Ester; 4 - {2 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - ethyl} - piperazin- - acetic acid Ester; 4 - {2 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - propyl} - piperazin- - acetic acid Ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - sulfinyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - sulfonyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [1 - (2 - Fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl thio] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [1 - (2 - Fluoride -4 - Methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl thio] - piperidine-1 - carboxylic acid butyl ester; 4 - [1 - (2 - fluoro- -4 - A Alkylsulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl thio] - piperidine-1 - acid 2 - methoxy - ester; 4 - [1 - ( 2 - fluoro- -4 - Methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl thio] - piperidine-1 - carboxylic acid 3,3 - dimethyl - butyl; 4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl thio] - piperidine-1 - acid 4 - methyl Base - E Ester; 4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl thio] - piperidine-1 - carboxylic acid ring propyl Ester; 4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl thio] - piperidine-1 - carboxylic acid Ring Ding Ylmethyl ester; 4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl thio] - piperidine-1 - acid 2 - Cyclopropyl - ester; (5 - bromo - furan-2 - yl) - {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4 - d] pyrimidin-4 - Yl thio] - piperidin-1 - yl} - methanone; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl oxy] - Piperidin-1 - yl} - (5 - morpholin-4 - yl methyl - furan-2 - yl) - methanone; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazole and [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid pentyl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4 -d] pyrimidine -4 - yloxy] - piperidine-1 - carboxylic acid 1 - ethyl - propyl; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d ] pyrimidine -4 - Yloxy] - piperidine-1 - acid 2 - ethyl - butyl; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - Yloxy] - piperidine-1 - carboxylic acid cyclopentyl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl Oxy] - piperidine-1 - acid 2 - pyrrolidin-1 - yl - ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine -4 - Yloxy] - piperidine-1 - acid 2 - morpholin-4 - yl - ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3, 4-d] Pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid ethyl ester; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - base Oxy] - piperidine-1 - carboxylic acid 2,2 - dimethyl - propyl; (5 - butyl - pyridin-2 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl) -1H- Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; ethyl - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl) -1H- Pyrazolo [3,4-d] pyrimidin-4 - yl] - (3,4,5,6 - tetrahydro-2H-[1,2 '] United pyridin-4 - ylmethyl) - amine; B yl - [1 - (2 - fluoro-4 - methyl Alkylsulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - (5'-trifluoromethyl-3, 4,5,6 - tetrahydro-2H-[ 1,2 '] bipyridine -4 - Yl methyl) - amine; [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - (5'-trifluoromethyl Base -3,4,5,6 - Tetrahydro-2H-[1,2 '] United pyridin-4 - yl) - amine; 4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4 -d] pyrimidin-4 - Yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 5'-fluoro-4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine - 4 - Base Oxy] -3,4,5,6 - tetrahydro-2H-[1,2 '] bipyridine; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3, 4-d] pyrimidin-4 - Yloxy]-5'-methyl-3, 4,5,6 - tetrahydro-2H-[1,2 '] bipyridine; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H - pyrazolo [3,4-d] pyrimidin-4 - yloxy]-6'-(trifluoromethyl) -3,4,5,6 - tetrahydro-2H-[1,2 '] bipyridine; [1 - ( 2 - fluoro-4 - methane sulfonyl - Phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - ylmethyl) - pyrrolidin-3 - yl] - Amine; [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - [1 - (3 - isopropyl - [ 1,2,4] oxadiazole -5 - Yl methyl) - pyrrolidin-3 - yl] - amine; (4 - ethyl - pyridin-2 - yl) - {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl )-1H-pyrazol Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; 1 - (2 - fluoro-4 - methanesulfonyl-- phenyl) -4 - [1 - (3 - isopropyl- - [1,2,4] oxadiazol-5 - ylmethyl) - pyrrolidin-3 - yloxy]-1H-pyrazolo [3,4-d] pyrimidine; 1 - (2 - fluoro - 4 - methane sulfonyl - Phenyl) -4 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - ylmethyl) - piperidin-4 - yloxy]-1H-pyrazolo [3,4-d] pyrimidine; (5'-fluoro-3 ,4,5,6 - tetrahydro-2H-[1,2 '] United pyridin-4 - yl) - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazol pyrazolo [3,4-d] pyrimidine -4 - Yl] - amine; (5 - bromo - pyridin-3 - yl) - {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4 -d] pyrimidin-4 - yl Oxy] - piperidin-1 - yl} - methanone; 3 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - Pyrrolidine-1 - carboxylic acid tert-butyl ester; 3 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl amino] - pyrrolidine Alkyl - 1 - carboxylate tert-butyl; 3 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - ylamino] - pyrrole Adamantan-1 - carboxylic acid isopropyl ester; (6 - chloro - pyridine - 3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - Yloxy] - piperidin-1 - yl} - methanone; (5 - chloro - pyridine - 3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] Pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine -4 - Yloxy] - piperidin-1 - yl} - (1 - methyl - 3 - (trifluoromethyl)-1H-pyrazol-4 - yl) - methanone; (2 - chloro - pyridin-4 - yl) - {4 - [1 - (4 - Methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; (4 - hydroxy - 3 - methoxy- - Phenyl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - ketone; (4 - Chloro-3 - nitro - phenyl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine -1 - Yl} - methanone; 1 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin- - yl} -3 - Methyl - butan-1 - one; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin - 1 - Yl} - (6 - pyrazol-1 - yl - pyridin-3 - yl) - methanone; (2 - hydroxy - pyridine - 3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl )-1H-pyrazol Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; (5,6 - Dichloro - pyridin-3 - yl) - {4 - [1 - (4 - methanesulfonyl - Phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; (5 - bromo - pyridin-3 - yl) - {4 - [1 - (4 - methane Sulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; 5 - {4 - [1 - (4 - methane sulfonyl - Phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carbonyl} - nicotinic acid; (1H-imidazol-4 - yl) - {4 - [ 1 - (4 - methane Sulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; 3 - [1 - (4 - methanesulfonyl- - Benzene Yl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - pyrrolidine-1 - carboxylic acid tert-butyl ester; {4 - [1 - (4 - methanesulfonyl - benzene Yl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - (6 - pyrrolidin-1 - yl - pyridin-3 - yl) - methyl ketone; (6 - iso Butylamino - pyridin-3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine pyridine -1 - Yl} - methanone; (6 - ethylamino - pyridin-3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4 - d] pyrimidine -4 - Yloxy] - piperidin-1 - yl} - methanone; (6 - cyclobutylamino - pyridin-3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl) -1H- Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; (6 - isopropylamino - pyridin-3 - yl) - {4 - [1 - (4 - methane Sulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; [6 - (1 - ethyl - propyl amino) - Pyridin-3 - yl] - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - yl} - A Ketone; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - [6 - (1 - propyl - Butylamino) - pyridin-3 - yl] - methanone; 5 - benzyloxy-2 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4 - d] pyrimidine -4 - yloxy] - piperidine-1 - carbonyl} - pyran-4 - one; benzo [c] isoxazol-3 - yl - {4 - [1 - (4 - methanesulfonyl - benzene Yl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; (4 - chloro - pyridin-2 - yl) - {4 - [1 - (4 - methanesulfonamide Acyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; (4 - iodo - pyridin-2 - yl) - {4 - [1 - (4 - Methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; 1 - {4 - [1 - (4 - methane sulfonic Acyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - butan-2 - one; 2 - (5 - bromo - pyridine - 3 - Yl) -1 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethanone; (6 - Fluoro - pyridin-2 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin - 1 - yl} - Methanone; (5 - fluoro - pyridin-2 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy yl] - piperidine -1 - Yl} - methanone; (6 - chloro - pyridin-2 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy Yl] - piperidin-1 - yl} - methanone; (2 - chloro-5 - fluoro - pyridin-3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazol pyrazolo [3,4-d] Pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine -4 - Yloxy] - piperidin-1 - yl} - [5 - (2 - methyl - pyrrolidin-1 - ylmethyl) - pyridin-3 - yl] - methanone; {4 - [1 - (4 - methane sulfonyl - Phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - (6 - methyl - pyridin-2 - yl) - methanone; 5 - {4 - [1 - (4 - Methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carbonyl} - nicotinonitrile; {4 - [1 - (4 - CH sulfur Acyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - (4 - methoxy - pyridin-2 - yl) - methyl ketone; (2 - Fluoro - pyridin-4 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin - 1 - yl} - Methanone; (2 - fluoro - pyridin-3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy yl] - piperidine -1 - Yl} - methanone; (6 - fluoro - pyridin-3 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy Yl] - piperidin-1 - yl} - methanone; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy ] - piperidine -1 - Yl} - (4 - methoxy - thiophen-3 - yl) - methanone; 2 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3, 4-d] pyrimidine -4 - Yloxy] - piperidine-1 - carbonyl} - pyran-4 - one; (5 - ethyl - pyridin-2 - yl) - {4 - [1 - (2 - fluoro-4 - CH sulfonyl - benzene Yl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; (4 - ethoxy - phenyl) - {4 - [ 1 - (2 - fluoro-4 - methyl Alkylsulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; {4 - [1 - (4 - CH sulfonyl - Phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - (5 - pyridin-2 - yl - thiophen-2 - yl) - methanone; (5 - amino Yl - pyridin-2 - yl) - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin - 1 - yl} - Methanone; (5 - amino - pyridin-2 - yl) - {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidine - 4 - yloxy Yl] - piperidin-1 - yl} - methanone; {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - Piperidin-1 - yl} - [5 - (3 - methyl - butylamino) - pyridin-2 - yl] - methanone; {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl yl)-1H- Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - (4 - (Trifluoromethoxy) - phenyl) - methanone; (5 - butyl - pyridine -2 - Yl) - {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - yl} - methanone; (5 - ethylamino - pyridin-2 - yl) - {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy Yl] - piperidin-1 - yl} - methanone; {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - Piperidin-1 - yl} - (5 - isopropoxy-methyl - pyridin-2 - yl) - methanone; (4 - difluoromethoxy - phenyl) - {4 - [1 - (2 - fluoro-4 - methane Sulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; {4 - [1 - (2 - fluoro - 4 - methanesulfonyl Yl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - (5 - isopropoxy - pyridin-2 - yl) - ketone; 5 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carbonyl} - pyridin - 2 - A Methyl; {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethyl acetate Esters; {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl } - (3 - trifluoromethyl Methoxy - phenyl) - methanone; 1 - (2 - fluoro-4 - methanesulfonyl-- phenyl) -4 - [1 - (3 - isopropyl - [1,2,4] oxadiazole -5 - yl) - piperidine -4 - Yloxy]-1H-pyrazolo [3,4-d] pyrimidine; 1 - (4 - chloro - phenyl) -2 - {4 - [1 - (4 - methanesulfonyl - phenyl )-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethanone; 2 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazole and [3,4-d] Pyrimidin-4 - yloxy] - piperidin-1 - yl} -1 - (3 - (trifluoromethyl) - phenyl) - ethanone; 4 - [1 - (2 - fluoro-4 - methanesulfonyl-- benzene Yl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy]-5'-isopropoxy-3 ,4,5,6 - tetrahydro-2H-[1,2 ' ] bipyridine; 1 - (4 - methyl Alkylsulfonyl - phenyl) -4 - [1 - (4 - (Trifluoromethoxy) - phenyl) - piperidin-4 - yloxy]-1H-pyrazolo [3,4-d] pyrimidine; 1 - (2 - Fluoro-4 - methanesulfonyl-- phenyl) -4 - [1 - (4 - (Trifluoromethoxy) - phenyl) - piperidin-4 - yloxy]-1H-pyrazolo [3,4 - d] pyrimidine Pyridine; 1 - (4 - chloro-3 - methyl - phenyl) -2 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine -4 - yloxy] - Piperidin-1 - yl} - ethanone; 1 - (3,4 - dichloro - phenyl) -2 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [ 3,4-d] pyrimidine -4 - Yloxy] - piperidin-1 - yl} - ethanone; 5'-bromo-4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4 - d] pyrimidin-4 - yl Oxy] -3,4,5,6 - tetrahydro-2H-[1,2 '] bipyridine; 1 - (2 - fluoro-4 - methanesulfonyl-- phenyl) -4 - [1 - (3 - trifluoromethoxy - benzene Yl) - piperidin-4 - yloxy]-1H-pyrazolo [3,4-d] pyrimidine; 4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3 ,4-d] Pyrimidin-4 - yloxy]-5'-trifluoromethyl-3, 4,5,6 - tetrahydro-2H-[1,2 '] bipyridine; 1 - (2,4 - dimethoxy- - Benzene Yl) -2 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidin-1 - yl} - ethyl ketone; 1 - (4 - difluoromethoxy - phenyl) -2 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine -1 - yl} - ethanone; 1 - (4 - diethylamino - phenyl) -2 - {4 - [1 - (4 - methanesulfonyl - phenyl)-1H-pyrazolo [3 ,4-d] pyrimidin -4 - yloxy] - piperidin-1 - yl} - ethanone; (2 - {4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [ 3,4-d] pyrimidine -4 - Yloxy] - piperidin-1 - yl} -5 - methyl - pyrimidin-4 - yl) - dimethyl - amine; 1 - (2 - fluoro-4 - methanesulfonyl-- phenyl Yl) -4 - [1 - (5 - methyl - 4 - pyrrolidin-1 - yl - pyrimidin-2 - yl) - piperidin-4 - yloxy]-1H-pyrazolo [3,4 - d] pyrimidine; 4 - [1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl thio] - piperidine-1 - carboxylic acid isopropyl ester ; 4 - [1 - (2 - methyl - 4 - propyl-amino - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl esters; 4 - [1 - (4 - isopropyl-amino-2 - methyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isobutyl propyl; 4 - [1 - (2 - methyl -4 - morpholin-4 - yl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - Isopropyl; 4 - {1 - [4 - (2 - methoxy - ethyl amino) -2 - methyl - phenyl]-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy} - piperidin-1 - A Isopropyl; 4 - (1 - {4 - [(2 - methanesulfonyl - ethyl) - methyl - amino] -2 - methyl - phenyl}-1H-pyrazolo [3,4 - d] pyrimidine -4 - Yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (4 - bromo - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy yl] - piperidine - 1 - carboxylate isopropyl; 4 - [1 - (4 - propyl-amino - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - Formic acid Propyl; 4 - [1 - (4 - isopropyl-amino - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester ; 4 - (1 - {4 - [4 - (2 - methanesulfonyl - ethyl) - piperazin-1 - yl] -2 - methyl - phenyl}-1H-pyrazolo [3,4-d ] pyrimidin-4 - yloxy Yl) - piperidine-1 - carboxylic acid isopropyl ester; 4 - (1 - {2 - methyl - 4 - [(tetrahydro - furan-2 - ylmethyl) - amino] - phenyl}-1H-pyrazol azole and [3,4-d] pyrimidin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (4 - cyclopropyl-2 - methyl - phenyl)-1H- pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {1 - [4 - (2 - dimethylamino - ethyl amino) -2 - methyl base - benzene Yl]-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (4 - morpholin-4 - yl - benzene yl)-1H- Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - ({[1 - (2 - fluoro-4 - methanesulfonyl-- phenyl) -1H- Pyrazolo [3,4-d] pyrimidin-4 - yl] - isopropyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [1 - (2 - fluoro-4 - morpholin-4 - Yl - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (2 - fluoro-4 - iso- propylamino - Phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - (1 - {4 - [(2 - methanesulfonyl- - B Yl) - methyl - amino] - phenyl}-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - {1 - [ 4 - (2 - Methoxy - ethylamino) - phenyl]-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - (1 - {4 - [(tetrahydro - furan-2 - ylmethyl) - amino] - phenyl}-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy) - piperidin-1 - A Isopropyl; 4 - (1 - {4 - [4 - (2 - methanesulfonyl - ethyl) - piperazin-1 - yl] - phenyl}-1H-pyrazolo [3,4-d ] pyrimidin-4 - yl Yloxy) - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (4 - amino - phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine -1 - Isopropyl; 4 - ({[1 - (2 - fluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3,4-d] pyrimidin-4 - yl] - isopropyl - ammonia Yl} - methyl) - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (5 - ethyl - pyrimidin-2 - yl) - piperidin-4 - yl thio] -1 - (2 - fluoro-4 - methane sulfonic Acyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine; 4 - [1 - (2 - fluoro-4 - sulfamoyl - phenyl)-1H-pyrazolo [3,4 - d] pyrimidin-4 - Yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (2 - fluoro-4 - propionyl-sulfamoyl - phenyl)-1H-pyrazolo [3,4-d] pyrimidine -4 - Yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (4 - cyano-2 - fluoro - phenyl)-1H-pyrazolo [3,4-d] pyrimidine -4 - yloxy Yl] - piperidine-1 - carboxylic acid isopropyl ester; 1 - (2,5 - difluoro-4 - methoxy - phenyl) -4 - [4 - (3 - isopropyl - [1, 4] oxadiazol-5 - yl) - Cyclohexyloxy]-1H-pyrazolo [3,4-d] pyrimidine; 4 - [1 - (2,5 - difluoro-4 - methanesulfonyl-- phenyl)-1H-pyrazolo [3 ,4-d] Pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (4 - fluoro-6 - methoxy - pyridine - 3 - yl)-1H-pyrazolo [3, 4-d] pyrimidine -4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (6 - methoxy-2 - methyl - pyridine - 3 - yl)-1H-pyrazolo [3 ,4-d] pyrimidin -4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (2,5 - difluoro-4 - sulfamoyl - phenyl)-1H-pyrazolo [3, 4-d] pyrimidine -4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (2 - fluoro-4 - hydroxy - phenyl)-1H-pyrazolo [3,4-d] pyrimidine -4 - yloxy Yl] - piperidine-1 - carboxylic acid isopropyl ester; 3 - fluoro-4 - {4 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidine -4 - yloxy] - pyrazol And [3,4-d] pyrimidin-1 - yl}-N-propionyl - benzenesulfonamide; 3 - fluoro-4 - {4 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperazine -4 - yloxy] - pyrazolo [3,4-d] pyrimidin-1 - yl} - benzonitrile; 3 - fluoro-4 - {4 - [1 - (3 - isopropyl - [ 1,2,4] oxadiazol-5 - Yl) - piperidin-4 - yloxy] - pyrazolo [3,4-d] pyrimidin-1 - yl} - benzenesulfonamide; 1 - (2,5 - difluoro-4 - methanesulfonyl-- benzene Yl) -4 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy]-1H-pyrazolo [3,4 -d] pyrimidine; 1 - (4 - fluoro-6 - Methoxy - pyridin-3 - yl) -4 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy]-1H - pyrazolo [3,4-d] Pyrimidine; 4 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy] -1 - (6 - methoxy-2- - methyl - pyridine-3 - Yl)-1H-pyrazolo [3,4-d] pyrimidine; 2,5 - difluoro-4 - {4 - [1 - (3 - isopropyl - [1,2,4] oxadiazol - 5 - yl) - piperidin-4 - yloxy Yl] - pyrazolo [3,4-d] pyrimidin-1 - yl} - benzenesulfonamide; 1 - (2 - fluoro-4 - methanesulfonyl-- phenyl) -4 - [4 - (3 - iso- propyl - [1,2,4] oxadiazol-5 - yl) - cyclohexyloxy]-1H-pyrazolo [3,4-d] pyrimidine; 3 - fluoro-4 - {4 - [4 - ( 3 - isopropyl - [1,2,4] Oxadiazol-5 - yl) - cyclohexyloxy] - pyrazolo [3,4-d] pyrimidin-1 - yl}-N-propionyl - benzenesulfonamide; 3 - fluoro- -4 - {4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - cyclohexyloxy] - pyrazolo [3,4-d] pyrimidine - 1 - yl} - benzonitrile; 3 - Fluoro-4 - {4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - cyclohexyloxy] - pyrazolo [3,4-d] pyrimidine -1 - yl} - benzenesulfonyl Amine; 1 - (2,5 - difluoro-4 - methanesulfonyl-- phenyl) -4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - cyclohexyloxy]-1H- Pyrazolo [3,4-d] pyrimidine; 1 - (4 - fluoro-6 - methoxy - pyridine - 3 - yl) -4 - [4 - (3 - isopropyl - [1,2,4 ] oxadiazol-5 - yl) - cyclohexyl Yloxy]-1H-pyrazolo [3,4-d] pyrimidine; 4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - cyclohexyl-yloxy yl] -1 - (6 - methyl -2 - methyl - pyridine - 3 - yl)-1H-pyrazolo [3,4-d] pyrimidine; 2,5 - difluoro-4 - {4 - [4 - (3 - isopropyl- - [1,2,4] oxadiazole -5 - Yl) - cyclohexyloxy] - pyrazolo [3,4-d] pyrimidin-1 - yl} - benzenesulfonamide; 4 - [1 - (2 - fluoro-4 - methoxy - phenyl yl)-1H- Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (4 - difluoromethoxy-2 - fluoro - phenyl) -1H-pyrazole Pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (2 - fluoro-4 - trifluoro-methoxy - phenyl) - 1H-pyrazol- And [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [1 - (2,5 - difluoro-4 - methoxy - phenyl) - 1H-pyrazolo [3,4-d] pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 3 - fluoro-4 - {4 - [1 - (3 - isopropyl - [1, 4] oxadiazol-5 - yl) - Piperidin-4 - yloxy] - pyrazolo [3,4-d] pyrimidin-1 - yl} - phenol; 1 - (2 - fluoro-4 - methoxy - phenyl) -4 - [1 - (3 - isopropyl- - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy]-1H-pyrazolo [3,4-d] pyrimidine; 1 - (4 - difluoromethoxy- -2 - fluoro - benzene Yl) -4 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy]-1H-pyrazolo [3,4 -d] pyrimidine; 1 - (2 - fluoro-4 - Trifluoromethoxy - phenyl) -4 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy]-1H- pyrazolo [3,4-d] Pyrimidine; 1 - (2,5 - difluoro-4 - methoxy - phenyl) -4 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy Yl]-1H-pyrazolo [3,4-d] pyrimidine; 3 - fluoro-4 - {4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl ) - cyclohexyloxy] - pyrazol And [3,4-d] pyrimidin-1 - yl} - phenol; 1 - (2 - fluoro-4 - methoxy - phenyl) -4 - [4 - (3 - isopropyl - [1 , 4] oxadiazol-5 - yl) - Cyclohexyloxy]-1H-pyrazolo [3,4-d] pyrimidine; 1 - (4 - difluoromethoxy-2 - fluoro - phenyl) -4 - [4 - (3 - isopropyl- - [1,2,4] Oxadiazol-5 - yl) - cyclohexyloxy]-1H-pyrazolo [3,4-d] pyrimidine;, and 1 - (2 - fluoro-4 - (Trifluoromethoxy) - phenyl Yl) -4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - cyclohexyloxy]-1H-pyrazolo [3,4-d] pyrimidine . ...

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D3 group): 4-[9-(6-methane sulfonyl-pyridin-3-yl)-9H-purine-6-base oxygen base]-piperidines-1-Tetryl formate.; 4-[9-(6-methane sulfonyl-pyridin-3-yl)-9H-purine-6-base oxygen base]-piperidines-1-yl }-pyridin-3-yl-ketone; 4-[9-(4-methane sulfonyl-phenyl)-9H-purine-6-base oxygen base]-piperidines-1-t-butyl formate; 4-[9-(6-methane sulfonyl-pyridin-3-yl)-9H-purine-6-base oxygen base]-piperidines-1-t-butyl formate and 4-[9-(2-fluoro-4-methane sulfonyl-phenyl)-9H-purine-6-base oxygen base]-piperidines-1-t-butyl formate.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D4 group): 4-[9-(2-fluoro-4-propiono sulfamoyl-phenyl)-9H-purine-6-base oxygen base]-piperidines-1-isopropyl formate; 4-[9-(4-cyano group-2-fluoro-phenyl)-9H-purine-6-base oxygen base]-piperidines-1-isopropyl formate; 4-[9-(2-fluoro-4-sulfamoyl-phenyl)-9H-purine-6-base oxygen base]-piperidines-1-isopropyl formate; 9-(2-fluoro-4-methane sulfonyl-phenyl)-6-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-the 9H-purine; 3-fluoro-4-{6-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-purine-9-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{6-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-purine-9-yl }-benzonitrile; 3-fluoro-4-{6-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-purine-9-yl }-benzsulfamide; 4-[9-(2,5-two fluoro-4-methane sulfonyl-phenyl)-9H-purine-6-base oxygen base]-piperidines-1-isopropyl formate; 4-[9-(4-fluoro-6-methoxyl group-pyridin-3-yl)-9H-purine-6-base oxygen base]-piperidines-1-isopropyl formate; 4-[9-(6-methoxyl group-2-methyl-pyridin-3-yl)-9H-purine-6-base oxygen base]-piperidines-1-isopropyl formate; 4-[9-(2,5-two fluoro-4-sulfamoyl-phenyl)-9H-purine-6-base oxygen base]-piperidines-1-isopropyl formate; 9-(2,5-two fluoro-4-methane sulfonyl-phenyl)-6-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-the 9H-purine; 9-(4-fluoro-6-methoxyl group-pyridin-3-yl)-6-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-the 9H-purine; 6-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-9-(6-methoxyl group-2-methyl-pyridin-3-yl)-9H-purine; 2,5-two fluoro-4-{6-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-purine-9-yl }-benzsulfamide; 9-(2-fluoro-4-methane sulfonyl-phenyl)-6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-the 9H-purine; 3-fluoro-4-{6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-purine-9-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-purine-9-yl }-benzonitrile; 3-fluoro-4-{6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-purine-9-yl }-benzsulfamide; 9-(2,5-two fluoro-4-methane sulfonyl-phenyl)-6-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-the 9H-purine; 9-(4-fluoro-6-methoxyl group-pyridin-3-yl)-6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-the 9H-purine; 6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-9-(6-methoxyl group-2-methyl-pyridin-3-yl)-9H-purine; With 2,5-two fluoro-4-{6-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-purine-9-yl }-benzsulfamide.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D5 group): 4-[3-(4-methane sulfonyl-phenyl)-3H-[1; 2; 3] triazol [4,5-d] pyrimidin-7-yl oxygen base]-piperidines-1-t-butyl formate.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D6 group): 3-(2-fluoro-4-methane sulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-3H-[1,2,3] triazol [4,5-d] pyrimidine; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-[1,2,3] triazol [4,5-d] pyrimidin-3-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-[1,2,3] triazol [4,5-d] pyrimidin-3-yl }-benzonitrile; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-[1,2,3] triazol [4,5-d] pyrimidin-3-yl }-benzsulfamide; 3-(2-fluoro-4-methane sulfonyl-phenyl)-7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-3H-[1,2,3] triazol [4,5-d] pyrimidine; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-[1,2,3] triazol [4,5-d] pyrimidin-3-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-[1,2,3] triazol [4,5-d] pyrimidin-3-yl }-benzonitrile; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-[1,2,3] triazol [4,5-d] pyrimidin-3-yl }-benzsulfamide; 3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-3H-[1,2,3] triazol [4,5-d] pyrimidine; 3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-3H-[1,2,3] triazol [4,5-d] pyrimidine; 7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-3-(6-methoxyl group-2-methyl-pyridin-3-yl)-3H-[1,2,3] triazol [4,5-d] pyrimidine; 2,5-two fluoro-4-{7-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-[1,2,3] triazol [4,5-d] pyrimidin-3-yl }-benzsulfamide; 4-[3-(2-fluoro-4-methane sulfonyl-phenyl)-3H-[1,2,3] triazol [4,5-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2-fluoro-4-propiono sulfamoyl-phenyl)-3H-[1,2,3] triazol [4,5-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(4-cyano group-2-fluoro-phenyl)-3H-[1,2,3] triazol [4,5-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2-fluoro-4-sulfamoyl-phenyl)-3H-[1,2,3] triazol [4,5-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-3H-[1,2,3] triazol [4,5-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-3H-[1,2,3] triazol [4,5-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(6-methoxyl group-2-methyl-pyridin-3-yl)-3H-[1,2,3] triazol [4,5-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2,5-two fluoro-4-sulfamoyl-phenyl)-3H-[1,2,3] triazol [4,5-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-3H-[1,2,3] triazol [4,5-d] pyrimidine; 3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-3H-[1,2,3] triazol [4,5-d] pyrimidine; 7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-3-(6-methoxyl group-2-methyl-pyridin-3-yl)-3H-[1,2,3] triazol [4,5-d] pyrimidine; With 2,5-two fluoro-4-{7-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-[1,2,3] triazol [4,5-d] pyrimidin-3-yl }-benzsulfamide.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D7 group): 4-[3-(4-methane sulfonyl-phenyl)-isoxazoles are [4,5-d] pyrimidin-7-yl oxygen base also]-piperidines-1-t-butyl formate.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D8 group): 4-({ ethyl-[3-(4-methane sulfonyl-phenyl)-isoxazoles are [4,5-d] pyrimidin-7-yl also]-amino }-methyl)-piperidines-1-t-butyl formate; 4-[3-(4-methane sulfonyl-phenyl)-isoxazoles are [4,5-d] pyrimidin-7-yl sulfenyl also]-piperidines-1-t-butyl formate; And 4-[3-(4-methane sulfonyl-phenyl)-isoxazoles [4,5-d] pyrimidin-7-yl oxygen base also]-piperidines-1-isopropyl formate.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D9 group): 4-[8-(2-fluoro-4-methane sulfonyl-phenyl)-[1,7] naphthyridines-4-base oxygen base]-piperidines-1-isopropyl formate.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D10 group): 4-[8-(2-fluoro-4-methane sulfonyl-phenyl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 4-[8-(4-methyl sulfenyl-phenyl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 4-[8-(4-methane sulfonyl-phenyl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 4-[8-(4-isopropoxy-phenyl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 4-[8-(4-bromo-2-fluoro-phenyl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 4-[8-(2-fluoro-4-propiono sulfamoyl-phenyl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 4-[8-(4-cyano group-2-fluoro-phenyl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 4-[8-(2-fluoro-4-sulfamoyl-phenyl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 4-[8-(2,5-two fluoro-4-methane sulfonyl-phenyl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 4-[8-(4-fluoro-6-methoxyl group-pyridin-3-yl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 4-[8-(6-methoxyl group-2-methyl-pyridin-3-yl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 4-[8-(2,5-two fluoro-4-sulfamoyl-phenyl)-quinolyl-4 oxygen base]-piperidines-1-isopropyl formate; 2,5-two fluoro-4-{4-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-quinoline-8-yl }-benzsulfamide; 4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-8-(6-methoxyl group-2-methyl-pyridin-3-yl)-quinoline; 8-(4-fluoro-6-methoxyl group-pyridin-3-yl)-4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-quinoline; 8-(2,5-two fluoro-4-methane sulfonyl-phenyl)-4-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-quinoline; 3-fluoro-4-{4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-quinoline-8-yl }-benzsulfamide; 3-fluoro-4-{4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-quinoline-8-yl }-benzonitrile; 3-fluoro-4-{4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-quinoline-8-yl }-N-propiono-benzsulfamide; 8-(2-fluoro-4-methane sulfonyl-phenyl)-4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-quinoline; 2,5-two fluoro-4-{4-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-quinoline-8-yl }-benzsulfamide; 4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-8-(6-methoxyl group-2-methyl-pyridin-3-yl)-quinoline; 8-(4-fluoro-6-methoxyl group-pyridin-3-yl)-4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-quinoline; 8-(2,5-two fluoro-4-methane sulfonyl-phenyl)-4-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-quinoline; 3-fluoro-4-{4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-quinoline-8-yl }-benzsulfamide; 3-fluoro-4-{4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-quinoline-8-yl }-benzonitrile; 3-fluoro-4-{4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-quinoline-8-yl }-N-propiono-benzsulfamide; And 8-(2-fluoro-4-methane sulfonyl-phenyl)-4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-quinoline.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D11 group): 4-[8-(2-fluoro-4-methane sulfonyl-phenyl)-pyrido [3,4-d] pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[8-(2-fluoro-4-propiono sulfamoyl-phenyl)-pyrido [3,4-d] pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[8-(4-cyano group-2-fluoro-phenyl)-pyrido [3,4-d] pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[8-(2-fluoro-4-sulfamoyl-phenyl)-pyrido [3,4-d] pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[8-(2,5-two fluoro-4-methane sulfonyl-phenyl)-pyrido [3,4-d] pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[8-(4-fluoro-6-methoxyl group-pyridin-3-yl)-pyrido [3,4-d] pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[8-(6-methoxyl group-2-methyl-pyridin-3-yl)-pyrido [3,4-d] pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[8-(2,5-two fluoro-4-sulfamoyl-phenyl)-pyrido [3,4-d] pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 8-(2-fluoro-4-methane sulfonyl-phenyl)-4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrido [3,4-d] pyrimidine; 3-fluoro-4-{4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrido [3,4-d] pyrimidine-8-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrido [3,4-d] pyrimidine-8-yl }-benzonitrile; 3-fluoro-4-{4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrido [3,4-d] pyrimidine-8-yl }-benzsulfamide; 8-(2,5-two fluoro-4-methane sulfonyl-phenyl)-4-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-pyrido [3,4-d] pyrimidine; 8-(4-fluoro-6-methoxyl group-pyridin-3-yl)-4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrido [3,4-d] pyrimidine; 4-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-8-(6-methoxyl group-2-methyl-pyridin-3-yl)-pyrido [3,4-d] pyrimidine; 2,5-two fluoro-4-{4-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-pyrido [3,4-d] pyrimidine-8-yl }-benzsulfamide; 8-(2-fluoro-4-methane sulfonyl-phenyl)-4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-pyrido [3,4-d] pyrimidine; 3-fluoro-4-{4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-pyrido [3,4-d] pyrimidine-8-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-pyrido [3,4-d] pyrimidine-8-yl }-benzonitrile; 3-fluoro-4-{4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-pyrido [3,4-d] pyrimidine-8-yl }-benzsulfamide; 8-(2,5-two fluoro-4-methane sulfonyl-phenyl)-4-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-pyrido [3,4-d] pyrimidine; 8-(4-fluoro-6-methoxyl group-pyridin-3-yl)-4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-pyrido [3,4-d] pyrimidine; 4-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-8-(6-methoxyl group-2-methyl-pyridin-3-yl)-pyrido [3,4-d] pyrimidine; With 2,5-two fluoro-4-{4-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-pyrido [3,4-d] pyrimidine-8-yl }-benzsulfamide.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D12 group): 3-(2-fluoro-4-methane sulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-pyrazolo [1,5-a] pyrimidine; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-pyrazolo [1,5-a] pyrimidin-3-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-pyrazolo [1,5-a] pyrimidin-3-yl }-benzonitrile; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-pyrazolo [1,5-a] pyrimidin-3-yl }-benzsulfamide; 3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-pyrazolo [1,5-a] pyrimidine; 3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-pyrazolo [1,5-a] pyrimidine; 7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-3-(6-methoxyl group-2-methyl-pyridin-3-yl)-pyrazolo [1,5-a] pyrimidine; 2,5-two fluoro-4-{7-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-pyrazolo [1,5-a] pyrimidin-3-yl }-benzsulfamide; 4-[3-(2-fluoro-4-methane sulfonyl-phenyl)-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2-fluoro-4-propiono sulfamoyl-phenyl)-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(4-cyano group-2-fluoro-phenyl)-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2-fluoro-4-sulfamoyl-phenyl)-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(6-methoxyl group-2-methyl-pyridin-3-yl)-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2,5-two fluoro-4-sulfamoyl-phenyl)-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 3-(2-fluoro-4-methane sulfonyl-phenyl)-7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrazolo [1,5-a] pyrimidine; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrazolo [1,5-a] pyrimidin-3-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrazolo [1,5-a] pyrimidin-3-yl }-benzonitrile; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrazolo [1,5-a] pyrimidin-3-yl }-benzsulfamide; 3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-pyrazolo [1,5-a] pyrimidine; 3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-pyrazolo [1,5-a] pyrimidine; 7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-3-(6-methoxyl group-2-methyl-pyridin-3-yl)-pyrazolo [1,5-a] pyrimidine; 2,5-two fluoro-4-{7-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-pyrazolo [1,5-a] pyrimidin-3-yl }-benzsulfamide; 4-[3-(2-fluoro-4-methane sulfonyl-phenyl)-2-methyl-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2-fluoro-4-propiono sulfamoyl-phenyl)-2-methyl-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(4-cyano group-2-fluoro-phenyl)-2-methyl-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2-fluoro-4-sulfamoyl-phenyl)-2-methyl-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-2-methyl-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-2-methyl-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(6-methoxyl group-2-methyl-pyridin-3-yl)-2-methyl-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2,5-two fluoro-4-sulfamoyl-phenyl)-2-methyl-pyrazolo [1,5-a] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 2,5-two fluoro-4-{7-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidin-3-yl }-benzsulfamide; 7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-3-(6-methoxyl group-2-methyl-pyridin-3-yl)-2-methyl-pyrazolo [1,5-a] pyrimidine; 3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidine; 3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidine; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidin-3-yl }-benzsulfamide; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidin-3-yl }-benzonitrile; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidin-3-yl }-N-propiono-benzsulfamide; 3-(2-fluoro-4-methane sulfonyl-phenyl)-7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidine; 3-(2-fluoro-4-methane sulfonyl-phenyl)-7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidine; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidin-3-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidin-3-yl }-benzonitrile; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidin-3-yl }-benzsulfamide; 3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidine; 3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidine; 7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-3-(6-methoxyl group-2-methyl-pyridin-3-yl)-2-methyl-pyrazolo [1,5-a] pyrimidine; With 2,5-two fluoro-4-{7-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-2-methyl-pyrazolo [1,5-a] pyrimidin-3-yl }-benzsulfamide.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D13 group): 4-[3-(2-fluoro-4-methane sulfonyl-phenyl)-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2-fluoro-4-propiono sulfamoyl-phenyl)-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(4-cyano group-2-fluoro-phenyl)-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2-fluoro-4-sulfamoyl-phenyl)-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(6-methoxyl group-2-methyl-pyridin-3-yl)-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2,5-two fluoro-4-sulfamoyl-phenyl)-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 3-(2-fluoro-4-methane sulfonyl-phenyl)-7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidine; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-3-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzonitrile; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzsulfamide; 3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidine; 3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidine; 7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-3-(6-methoxyl group-2-methyl-pyridin-3-yl)-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidine; 2,5-two fluoro-4-{7-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzsulfamide; 3-(2-fluoro-4-methane sulfonyl-phenyl)-7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidine; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-3-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzonitrile; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzsulfamide; 3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidine; 3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidine; 7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-3-(6-methoxyl group-2-methyl-pyridin-3-yl)-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidine; With 2,5-two fluoro-4-{7-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-1-methyl isophthalic acid H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzsulfamide.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US2004/022417 number comprises following chemical compound according to formula (IV) (being referred to herein as the D14 group): 4-[3-(2-fluoro-4-methane sulfonyl-phenyl)-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2-fluoro-4-propiono sulfamoyl-phenyl)-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(4-cyano group-2-fluoro-phenyl)-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2-fluoro-4-sulfamoyl-phenyl)-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(6-methoxyl group-2-methyl-pyridin-3-yl)-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-(2,5-two fluoro-4-sulfamoyl-phenyl)-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-7-yl oxygen base]-piperidines-1-isopropyl formate; 3-(2-fluoro-4-methane sulfonyl-phenyl)-7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidine; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-3-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzonitrile; 3-fluoro-4-{7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzsulfamide; 3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-7-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidine; 3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidine; 7-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-3-(6-methoxyl group-2-methyl-pyridin-3-yl)-2-methyl-2H-pyrazolo [4,3-d] pyrimidine; 2,5-two fluoro-4-{7-[1-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-piperidin-4-yl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzsulfamide; 3-(2-fluoro-4-methane sulfonyl-phenyl)-7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidine; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-3-yl }-N-propiono-benzsulfamide; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzonitrile; 3-fluoro-4-{7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzsulfamide; 3-(2,5-two fluoro-4-methane sulfonyl-phenyl)-7-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidine; 3-(4-fluoro-6-methoxyl group-pyridin-3-yl)-7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidine; 7-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-cyclohexyl oxygen base]-3-(6-methoxyl group-2-methyl-pyridin-3-yl)-2-methyl-2H-pyrazolo [4,3-d] pyrimidine; With 2,5-two fluoro-4-{7-[4-(3-isopropyl-[1,2,4] oxadiazole-5-yl)-cyclohexyl oxygen base]-2-methyl-2H-pyrazolo [4,3-d] pyrimidin-3-yl }-benzsulfamide.

The case description of GPR119 agonist in international application case PCT/US2005/019318 number (open) with WO2005/121121, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/US2005/019318 number is the formula V chemical compound:

Or its N-oxide;

Wherein:

A ₁And A ₂Be the C that replaces through one or more substituent groups according to circumstances independently _1-3Alkylidene, described substituent group is independently selected from by C _1-6Alkyl, C _1-6The group that alkoxyl and carboxyl are formed;

D is CR ₁R ₂Or NR ₂, R wherein ₁Be selected from by H, C _1-6Alkyl, C _1-6The group that alkoxyl, halogen and hydroxyl are formed;

E is N, C or CR ₃, R wherein ₃Be H or C _1-6Alkyl;

When E is N or CR ₃The time,

Be singly-bound, or when E is C,

Be two keys;

K does not exist, and is the C that replaces through one or more substituent groups according to circumstances _3-6Cycloalkylidene or C _1-3Alkylidene, described substituent group is independently selected from by C _1-6Alkyl, C _1-6The group that alkoxyl, carboxyl, cyano group and halogen are formed;

Q ₁Be NR ₄, O, S, S (O) or S (O) ₂, R wherein ₄Be H, C _1-6Acyl group, C _1-6Alkyl, C _2-6Thiazolinyl, C _2-6Alkynyl, C _3-7Cycloalkyl or C _3-7Cycloalkyl-C _1-3Alkylidene, wherein said C _1-6Alkyl replaces through one or more substituent groups according to circumstances, and described substituent group is independently selected from by C _1-6Acyl group, C _1-6Acyloxy, C _2-6Thiazolinyl, C _1-6Alkoxyl, C _1-6Alkyl, C _1-6Alkyl amino, C _1-6Alkyl formamides, C _2-6Alkynyl, C _1-6Alkyl sulfonamide, C _1-6Alkyl sulphinyl, C _1-6Alkyl sulphonyl, C _1-6Alkyl sulfenyl, C _1-6Alkylthio Methanamide, C _1-6Alkyl sulfide urea groups, C _1-6Alkyl urea groups, amino, two-C _1-6Alkyl amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, two-C _1-6Alkyl formamides, two-C _1-6Alkyl sulfonamide, two-C _1-6Alkylthio formamido, C _1-6Halogen alkoxyl, C _1-6Alkylhalide group, halogen, C _1-6Alkylhalide group sulfinyl, C _1-6Alkylhalide group sulfonyl, C _1-6The group that alkylhalide group sulfenyl, hydroxyl, hydroxyl amino and nitro are formed;

Q ₂Not existing, is NR ₅Or O, wherein R ₅Be H, C _1-6Acyl group, C _1-6Alkyl, C _2-6Thiazolinyl, C _2-6Alkynyl, C _3-7Cycloalkyl or C _3-7Cycloalkyl-C _1-3Alkylidene, wherein said C _1-6Alkyl replaces through one or more substituent groups according to circumstances, and described substituent group is selected from by C _1-6Acyl group, C _1-6Acyloxy, C _2-6Thiazolinyl, C _1-6Alkoxyl, C _1-6Alkyl, C _1-6Alkyl amino, C _1-6Alkyl formamides, C _2-6Alkynyl, C _1-6Alkyl sulfonamide, C _1-6Alkyl sulphinyl, C _1-6Alkyl sulphonyl, C _1-6Alkyl sulfenyl, C _1-6Alkylthio Methanamide, C _1-6Alkyl sulfide urea groups, C _1-6Alkyl urea groups, amino, two-C _1-6Alkyl amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, two-C _1-6Alkyl formamides, two-C _1-6Alkyl sulfonamide, two-C _1-6Alkylthio formamido, C _1-6Halogen alkoxyl, C _1-6Alkylhalide group, halogen, C _1-6Alkylhalide group sulfinyl, C _1-6Alkylhalide group sulfonyl, C _1-6The group that alkylhalide group sulfenyl, hydroxyl, hydroxyl amino and nitro are formed;

W is N or CH;

X is N or CR ₆

Y is N or CR ₇

Z is N or CR ₈

V does not exist, and is C _1-3Inferior assorted alkyl or C _1-3Alkylidene, wherein each group replaces through one or more substituent groups according to circumstances, and described substituent group is independently selected from by C _1-3Alkyl, C _1-6Alkoxyl, carboxyl, cyano group, C _1-3The group that alkylhalide group and halogen are formed;

R ₆, R ₇And R ₈Be selected from independently of one another by H, C _1-6Acyl group, C _1-6Acyloxy, C _2-6Thiazolinyl, C _1-6Alkoxyl, C _1-6Alkyl, C _1-6Alkyl amino, C _1-6Alkyl formamides, C _2-6Alkynyl, C _1-6Alkyl sulfonamide, C _1-6Alkyl sulphinyl, C _1-6Alkyl sulphonyl, C _1-6Alkyl sulfenyl, C _1-6Alkylthio Methanamide, C _1-6Alkyl sulfide urea groups, C _1-6Alkyl urea groups, amino, two-C _1-6Alkyl amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, two-C _1-6Alkyl formamides, two-C _1-6Alkyl sulfonamide, two-C _1-6Alkylthio formamido, C _1-6Halogen alkoxyl, C _1-6Alkylhalide group, halogen, C _1-6Alkylhalide group sulfinyl, C _1-6Alkylhalide group sulfonyl, C _1-6The group that alkylhalide group sulfenyl, hydroxyl, hydroxyl amino and nitro are formed, wherein said C _2-6Thiazolinyl, C _1-6Alkyl, C _2-6Alkynyl and C _3-6Cycloalkyl replaces through one or more substituent groups separately according to circumstances, and described substituent group is independently selected from by C _1-6Acyl group, C _1-6Acyloxy, C _2-6Thiazolinyl, C _1-6Alkoxyl, C _1-6Alkyl, C _1-6Alkyl amino, C _1-6Alkyl formamides, C _2-6Alkynyl, C _1-6Alkyl sulfonamide, C _1-6Alkyl sulphinyl, C _1-6Alkyl sulphonyl, C _1-6Alkyl sulfenyl, C _1-6Alkylthio Methanamide, C _1-6Alkyl sulfide urea groups, C _1-6Alkyl urea groups, amino, two-C _1-6Alkyl amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, two-C _1-6Alkyl formamides, two-C _1-6Alkyl sulfonamide, two-C _1-6Alkylthio formamido, C _1-6Halogen alkoxyl, C _1-6Alkylhalide group, halogen, C _1-6Alkylhalide group sulfinyl, C _1-6Alkylhalide group sulfonyl, C _1-6The group that alkylhalide group sulfenyl, hydroxyl, hydroxyl amino and nitro are formed;

Ar is according to circumstances through R ₉-R ₁₃The aryl or the heteroaryl that replace;

R ₉Be selected from by C _1-6Acyl group, C _1-6Acyloxy, C _2-6Thiazolinyl, C _1-6Alkoxyl, C _1-6Alkyl, C _1-6Alkyl amino, C _1-6Alkyl formamides, C _2-6Alkynyl, C _1-6Alkyl sulfonamide, C _1-6Alkyl sulphinyl, C _1-6Alkyl sulphonyl, C _1-6Alkyl sulfenyl, C _1-6Alkylthio Methanamide, C _1-6Alkyl sulfide urea groups, C _1-6Alkyl urea groups, amino, aryl, aryl carbonyl, aryl sulfonyl, two-C _1-6Alkyl amino, amidino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, two-C _1-6Alkyl formamides, two-C _1-6Alkyl sulfonamide, two-C _1-6Alkylthio formamido, guanidine, C _1-6Halogen alkoxyl, C _1-6Alkylhalide group, halogen, C _1-6Alkylhalide group sulfinyl, C _1-6Alkylhalide group sulfonyl, C _1-6Alkylhalide group sulfenyl, heterocyclic radical, heterocyclic radical sulfonyl, heteroaryl, hydroxyl, hydroxyl amino, nitro, C _3-6The group that oxo-cycloalkyl, phenoxy group, sulfonamide, sulfonic acid and mercaptan are formed; And each available R wherein ₉Replace through one or more substituent groups according to circumstances, described substituent group is independently selected from by C _1-6Acyl group, C _1-6Acyl group sulfonamide, C _1-6Acyloxy, C _2-6Thiazolinyl, C _1-6Alkoxyl, C _1-6Alkyl, C _1-6Alkyl amino, C _1-6Alkyl formamides, C _2-6Alkynyl, C _1-6Alkyl sulfonamide, C _1-6Alkyl sulphinyl, C _1-6Alkyl sulphonyl, C _1-6Alkyl sulfenyl, C _1-6Alkylthio Methanamide, C _1-6Alkyl sulfide urea groups, C _1-6Alkyl urea groups, amino, aryl, aryl carbonyl, aryl sulfonyl, two-C _1-6Alkyl amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, two-C _1-6Alkyl formamides, two-C _1-6Alkyl sulfonamide, two-C _1-6Alkylthio formamido, C _1-6Halogen alkoxyl, C _1-6Alkylhalide group, halogen, C _1-6Alkylhalide group sulfinyl, C _1-6Alkylhalide group sulfonyl, C _1-6The group that alkylhalide group sulfenyl, heteroaryl, heteroaryl carbonyl, heteroarylsulfonyl, heterocyclic radical, hydroxyl, hydroxyl amino and nitro are formed;

R ₁₀-R ₁₃Be independently selected from by C _1-6Acyl group, C _1-6Acyloxy, C _2-6Thiazolinyl, C _1-6Alkoxyl, C _1-6Alkyl, C _1-6Alkyl amino, C _1-6Alkyl formamides, C _2-6Alkynyl, C _1-6Alkyl sulfonamide, C _1-6Alkyl sulphinyl, C _1-6Alkyl sulphonyl, C _1-6Alkyl sulfenyl, C _1-6Alkylthio Methanamide, C _1-6Alkyl sulfide urea groups, C _1-6Alkyl urea groups, amino, two-C _1-6Alkyl amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, two-C _1-6Alkyl formamides, two-C _1-6Alkyl sulfonamide, two-C _1-6Alkylthio formamido, C _1-6Halogen alkoxyl, C _1-6Alkylhalide group, halogen, C _1-6Alkylhalide group sulfinyl, C _1-6Alkylhalide group sulfonyl, C _1-6The group that alkylhalide group sulfenyl, hydroxyl, hydroxyl amino, nitro and mercaptan are formed; Or two adjacent groups form 5 yuan, 6 yuan or 7 yuan of cycloalkyl, cycloalkenyl group or heterocyclic radicals with the atom of its bond, and wherein said 5 yuan, 6 yuan or 7 yuan of groups replace through halogen or oxo base according to circumstances; And

R ₂Be selected from by H, C _1-6Acyl group, C _1-6Acyloxy, C _2-6Thiazolinyl, C _1-6Alkoxyl, C _1-6Alkyl, C _1-6Alkyl amino, C _1-6Alkyl formamides, C _2-6Alkynyl, C _1-6Alkyl sulfonamide, C _1-6Alkyl sulphinyl, C _1-6Alkyl sulphonyl, C _1-6Alkyl sulfenyl, C _1-6Alkylthio Methanamide, C _1-6Alkyl sulfide urea groups, C _1-6Alkyl urea groups, amino, aryl, aryl carbonyl, aryloxy group, two-C _1-6Alkyl amino, amidino, C _1-6Alkoxy carbonyl group, C _3-7Cyclo alkoxy carbonyl, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, two-C _1-6Alkyl formamides, two-C _1-6Alkyl sulfonamide, two-C _1-6Alkylthio formamido, guanidine, C _1-6Halogen alkoxyl, C _1-6Alkylhalide group, halogen, C _1-6Alkylhalide group sulfinyl, C _1-6Alkylhalide group sulfonyl, C _1-6Alkylhalide group sulfenyl, heteroaryl, heteroaryl-C _1-3The group that alkylidene, heteroaryl carbonyl, heteroaryloxy, heterocyclic radical Methanamide, hydroxyl, hydroxyl amino and nitro are formed; Each available R wherein ₂Replace through one or more substituent groups according to circumstances, described substituent group is independently selected from by C _1-6Acyl group, C _1-6Acyloxy, C _2-6Thiazolinyl, C _1-6Alkoxyl, C _1-6Alkyl, C _1-6Alkyl amino, C _1-6Alkyl formamides, C _2-6Alkynyl, C _1-6Alkyl sulfonamide, C _1-6Alkyl sulphinyl, C _1-6Alkyl sulphonyl, C _1-6Alkyl sulfenyl, C _1-6Alkylthio Methanamide, C _1-6Alkyl sulfide urea groups, C _1-6Alkyl urea groups, amino, aryl, two-C _1-6Alkyl amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, two-C _1-6Alkyl formamides, two-C _1-6Alkyl sulfonamide, two-C _1-6Alkylthio formamido, C _1-6Halogen alkoxyl, C _1-6Alkylhalide group, halogen, C _1-6Alkylhalide group sulfinyl, C _1-6Alkylhalide group sulfonyl, C _1-6The group that alkylhalide group sulfenyl, heterocyclic radical, heteroaryl, hydroxyl, hydroxyl amino and nitro are formed, and C wherein _1-6Alkyl further replaces through one or more substituent groups according to circumstances, and described substituent group is independently selected from by C _1-6Acyl group, C _1-6Alkoxyl, C _1-6Alkyl amino, C _1-6Alkyl formamides, C _1-6Alkyl sulfonamide, C _1-6Alkyl sulphinyl, C _1-6Alkyl sulphonyl, C _1-6Alkyl sulfenyl, C _1-6Alkyl urea groups, amino, two-C _1-6Alkyl amino, C _1-6Alkoxy carbonyl group, Methanamide, carboxyl, cyano group, C _3-6Cycloalkyl, two-C _1-6Alkyl formamides, two-C _1-6Alkyl sulfonamide, C _1-6Halogen alkoxyl, C _1-6Alkylhalide group, halogen, C _1-6Alkylhalide group sulfinyl, C _1-6Alkylhalide group sulfonyl, C _1-6The group that alkylhalide group sulfenyl, heterocyclic radical, hydroxyl, hydroxyl amino and nitro are formed.

International Application No. PCT/US2005/019318 disclosed in the No. Specific examples of GPR119 agonists include the Column according to formula (V) compound (referred to herein as Group E1): 4 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperazine -1 - yl] -6 - (4 - methanesulfonyl-- phenoxy) - pyrimidine; {6 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl ) - piperidin-1 - yl] - Pyrimidin-4 - yl} - (4 - methanesulfonyl - phenyl) - amine; 4 - {[6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - methyl Yl - amino} - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - methyl - amino Yl} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - methyl - amino} - Methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2,5 - difluoro - benzyl-amino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine - 1 - carboxylate tert-butyl ester; 4 - [({6 - [(benzo [1,3] dioxol-5 - ylmethyl) - amino] - pyrimidin-4 - yl} - methyl Base - Ammonia Yl) - methyl] - piperidine-1 - carboxylic acid tert-butyl ester; (2 - fluoro-4 - methanesulfonyl-- phenyl) - {6 - [4 - (3 - fluoro - phenoxy) - piperidine -1 - Yl] - pyrimidin-4 - yl} - amine; 4 - ({Methyl - [6 - (2 - pyridin-4 - yl - ethylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidin-1 - Carboxylic acid tert-butyl ester; 4 - ({Methyl - [6 - (2 - pyridin-3 - yl - ethylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert- Butyl; 4 - [(methyl - {6 - [(pyridin-3 - yl methyl) - amino] - pyrimidin-4 - yl} - amino) - methyl] - piperidine-1 - carboxylic acid tert-butyl ester ; 4 - [({6 - [(2 - fluoro-4 - methanesulfonyl-- phenyl) - methyl - amino] - pyrimidin-4 - yl} - methyl - amino) - methyl] - piperidine-1 - formic acid Tert-butyl ester; 4 - ({[6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid Titanium Dioxide; 4 - ({[6 - (4 - cyano-2 - fluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert- Ding Ester; 4 - [({6 - [4 - (2 - methanesulfonyl - ethyl) - phenylamino] - pyrimidin-4 - yl} - methyl - amino) - methyl] - piperidine-1 - formic acid Tert-butyl ester; 4 - ({[6 - (4 - ethylthio - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl Ester; 4 - ({[6 - (4 - isopropyl-thio - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (4 - ethyl-sulfamoyl - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({Methyl - [6 - (4 - methyl-sulfamoyl - phenylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (4 - dimethylsulfamoyl group - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({Methyl - [6 - (4 - methyl sulfamoyl methyl - phenylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl Ester; 4 - ({methyl - [6 - (4 - sulfamoyl - phenylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({Methyl - [6 - (4 - [1,2,4] triazol-1 - yl - phenylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine - carboxylic acid tert-butyl ester; 4 - ({Methyl - [6 - (4 - [1,2,4] triazol-1 - yl methyl - phenylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine - 1 - carboxylate tert-butyl Ester; 4 - [(methyl - {6 - [4 - (2 - [1,2,4] triazol-1 - yl - ethyl) - phenylamino] - pyrimidin-4 - yl} - amino) - methyl] - piperidine-1 - Carboxylic acid tert-butyl ester; 4 - ({[6 - (Benzo [1,3] dioxol-5 - ylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - Piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (6 - methanesulfonyl-- pyridin-3 - ylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - Piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (3,5 - dimethoxy - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine pyridine - 1 - carboxylate tert-butyl ester; 4 - [(methyl - {6 - [4 - (2 - oxo - oxazol-4 - ylmethyl) - phenylamino] - pyrimidin-4 - yl} - amino) - Methyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [({6 - [4 - (1,1 - dioxo-1λ6-thiomorpholin-4 - ylmethyl) - phenylamino ] - ethyl -4 - yl} - methyl - amino) - methyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({Methyl - [6 - (4 - pyrazol-1 - yl - phenylamino ) - ethyl -4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2,2 - difluoro - benzo [1,3] dioxa cyclopentyl-5 - Ylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({Methyl - [6 - (4 - trifluoromethanesulfonyl Yl - phenylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [(methyl - {6 - [4 - (morpholin-4 - sulfonyl Yl) - phenylamino] - pyrimidin-4 - yl} - amino) - methyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [(methyl - {6 - [2 - (pyridin-2 - carbonyl Yl) - phenylamino] - pyrimidin-4 - yl} - amino) - methyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2 - fluoro-5 - methanesulfonyl-- Phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; N-ethyl-3 - fluoro-4 - [6 - (methyl - piperazine -4 - yl methyl - amino) - pyrimidin-4 - ylamino] - benzenesulfonamide; 3 - fluoro-N-isopropyl-4 - [6 - (methyl - piperidin-4 - yl methyl - Amino) - pyrimidin-4 - ylamino] - benzenesulfonamide; 4 - ({[6 - (3,4 - difluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl Yl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2,6 - difluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine - 1 - carboxylate tert-butyl ester; 4 - ({[6 - (2,5 - difluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylate Butyl; 4 - ({[6 - (2,3 - difluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({Methyl - [6 - (2,3,5 - trifluoro - phenylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2 - fluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2 - fluoro-4 - Methyl - phenyl-amino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (3 - chloro-2 - fluoro- - Benzene Ylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2,4 - difluoro - phenylamino) - Pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [(methyl - {6 - [2 - (1 - oxy - pyridin-3 - yl) - B Ylamino] - pyrimidin-4 - yl} - amino) - methyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [(methyl - {6 - [2 - (1 - oxy - pyridin-3 - yl) - Ethylamino] - pyrimidin-4 - yl} - amino) - methyl] - piperidine-1 - carboxylic acid isobutyl ester; 4 - ({[6 - (2,5 - difluoro - phenylamino) - pyrimidine -4 - Yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid isobutyl ester; 4 - ({[6 - (4 - cyano-2 - fluoro - phenylamino) - pyrimidin - 4 - yl] - Methyl - amino} - methyl) - piperidine-1 - carboxylic acid isobutyl ester; 4 - [({6 - [2 - (2 - fluoro - phenoxy) - ethylamino] - pyrimidin-4 - yl } - A Yl - amino) - methyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2 - fluoro - phenoxy) - pyrimidin-4 - yl] - methyl - amino} - methyl yl) - Piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2,5 - difluoro - phenoxy) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine - 1 - carboxylic acid Tert-butyl ester; 4 - [({6 - [2 - (2 - chloro - phenoxy) - ethylamino] - pyrimidin-4 - yl} - methyl - amino) - methyl] - piperidine-1 - tert- Butyl; 4 - ({[6 - (2 - chloro - phenoxy) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [({6 - [2 - (4 - fluoro - phenoxy) - propyl amino] - pyrimidin-4 - yl} - methyl - amino) - methyl] - piperidine-1 - carboxylic acid tert-butyl esters; 4 - ({[6 - (4 - ethyl-sulfamoyl-2 - fluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl Ester; 4 - ({[6 - (2 - fluoro-4 - isopropyl-sulfamoyl - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - formic acid Tert-butyl ester; 4 - ({[6 - (4 - cyano-2 ,5 - difluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine - tert- Butyl; 4 - ({[6 - (4 - bromo-2 ,5 - difluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (5 - carboxy-2 - fluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (6 - methoxy - pyridin-3 - ylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2,6 - dimethoxy - pyridin-3 - ylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl esters; 6 - {6 - [(1 - tert-butoxycarbonyl group - piperidin-4 - yl methyl) - methyl - amino] - pyrimidin-4 - yl amino} - nicotinic acid; 4 - ({[6 - (6 - acetyl Amino - pyridin-3 - ylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (5 - fluoro - pyridine -2 - ylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (4 - cyano-2 - ethyl - Phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (4 - butyryl - phenylamino Yl) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (5 - bromo-3 - methyl - pyridin-2 - Ammonia Yl) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (3 - bromo-5 - methyl - pyridin-2 - Ammonia Yl) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({Methyl - [6 - (5 - (trifluoromethyl) - pyridin - 2 - Ylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (4 - bromo - 2 - fluoro - phenylamino) - pyrimidine -4 - Yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (3 - carboxy-4 - fluoro - phenylamino) - pyrimidin-4 - yl] - Methyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (4 - ethoxycarbonyl-2 - fluoro - phenylamino) - pyrimidin-4 - yl] - Methyl - amino} - methyl) - piperidine-1 - carboxylic acid isobutyl ester; 4 - ({[6 - (4 - carboxy-2 - fluoro - phenylamino) - pyrimidin-4 - yl] - methyl - Amino} - methyl) - piperidine-1 - carboxylic acid isobutyl ester; 4 - ({[6 - (4 - cyano-2 - fluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino- } - Methyl) - piperidine-1 - carboxylic acid isopropyl ester; 4 - ({[6 - (4 - cyano-2 - fluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl yl) - Piperidine-1 - carboxylic acid butyl ester; 4 - ({[6 - (4 - cyano-2 - fluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine -1 - Cyclopropyl methyl formate; {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - piperazin-1 - yl} - acetate; (2 - fluoro-4 - methanesulfonyl-- phenyl) - {6 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - ylmethyl) - piperazin-1 - yl] - pyrimidin-4 - Yl} - amine; 4 - ({[6 - (2,5 - difluoro-4 - hydroxy - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine - Formic acid Butyl; 4 - ({[6 - (4 - ethyl-carbamoyl-2 - fluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - Isobutyl; 4 - [({6 - [2 - fluoro -4 - (N-hydroxy-carbamimidoyl) - phenylamino] - pyrimidin-4 - yl} - methyl - amino) - methyl] - piperazine -1 - carboxylic acid isobutyl ester; 4 - ({[6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - Piperidine-1 - acid 3 - methyl - ester; 4 - ({[6 - (2,5 - difluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - methyl - ammonia Yl} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - methyl - Amino} - methyl) - piperidine-1 - carboxylic acid isopropyl ester; (5 - butyl - pyridin-2 - yl) - [4 - ({[6 - (2 - fluoro-4 - methanesulfonyl-- phenyl Ammonia Yl) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidin-1 - yl] - methanone; N-(2 - fluoro-4 - methanesulfonyl-- phenyl)-N ' - (5'- Fluoro-3 ,4,5,6 - tetrahydro-2H-[1,2 '] United pyridin-4 - ylmethyl)-N'-methyl - pyrimidine; 4, 6 - diamine; 4 - ( {[6 - (4 - amidino-2 - Fluoro - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid isobutyl ester; 4 - ({[6 - (2 - fluoro-4 - methanesulfonamide acyl Yl - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid butyl ring; 4 - [6 - (2 - fluoro-4 - methanesulfonyl- - Phenylamino) - pyrimidin-4 - ylamino] - piperidine-1 - carboxylic acid tert-butyl ester; N-(2 - fluoro-4 - methanesulfonyl-- phenyl)-N'-[1 - (3 - Isopropyl - [1,2,4] oxadiazol-5 - ylmethyl) - piperidin-4 - yl methyl]-N'-methyl - pyrimidine; 4, 6 - diamine; 4 - ({[6 - (2 - fluoro-4 - Methanesulfonyl - phenylamino) - pyrimidin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid 1 - ethyl - propyl; 4 - ({ethyl- - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({ethyl- - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid isopropyl ester; 4 - ({[6 - (4 - cyano-2 ,5 - difluoro - phenylamino) - pyrimidin-4 - yl] - ethyl - amino} - methyl) - piperidine-1 - carboxylic acid isopropyl esters; 4 - ({[6 - (4 - amino-2 ,5 - difluoro - phenoxy) - pyrimidin-4 - yl] - ethyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester ; 4 - ({[6 - (2,5 - difluoro-4 - methoxy - phenyl-amino) - pyrimidin-4 - yl] - ethyl - amino} - methyl) - piperidine-1 - carboxylic acid tert- butyl; 4 - ({[6 - (2,5 - difluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - ethyl - amino} - methyl) - piperidine-1 - carboxylic acid tert- Ding Ester; 4 - ({Ethyl - [6 - (2,4,5 - trifluoro - phenylamino) - pyrimidin-4 - yl] - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester ; (2 - Fluoro-4 - methanesulfonyl-- phenyl) - {6 - [4 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl] - pyrimidine -4 - yl} - amine; 4 - [(ethyl - {6 - [4 - (N-amidino-ethyl) -2,5 - difluoro - phenylamino] - pyrimidin-4 - yl} - amino) - methyl] - piperazine -1 - carboxylic acid Isopropyl; 4 - ({[6 - (4 - bromo-2 ,5 - difluoro - phenylamino) - pyrimidin-4 - yl] - ethyl - amino} - methyl) - piperidine-1 - tert-butyl Ester; 4 - [({6 - [5 - (2 - amino - ethyl)-4 - cyano-2 - fluoro - phenylamino] - pyrimidin-4 - yl} - ethyl - amino) - A yl] - piperazine -1 - carboxylic acid isopropyl ester; {1 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - piperidin-4 - yl} - acetic acid methyl Ester; 3 - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl] - piperazin-1 - yl} - propionic acid ethyl ester; (2 - fluoro- -4 - A Alkylsulfonyl - phenyl) - {6 - [4 - (4 - iso-butyl - phenyl) - piperidin-1 - yl] - pyrimidin-4 - yl} - amine; (2 - fluoro-4 - CH sulfonyl - Phenyl) - {6 - [4 - (4 - isopropyl - phenyl) - piperidin-1 - yl] - pyrimidin-4 - yl} - amine; {6 - [4 - (3 - cyclopropyl- methyl - [1,2,4] oxadiazole -5 - yl) - piperidin-1 - yl] - pyrimidin-4 - yl} - (2 - fluoro-4 - methanesulfonyl-- phenyl) - amine; (2 - fluoro-4 - methanesulfonyl-- benzene Yl) - {6 - [4 - (3 - isobutyl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl] - pyrimidin-4 - yl} - amine; ( 2 - fluoro-4 - methane sulfonyl - Phenyl) - {6 - [4 - (4 - isopropoxy - phenyl) - piperazin-1 - yl] - pyrimidin-4 - yl} - amine; (2 - fluoro-4 - methanesulfonyl-- benzene Yl) - {6 - [4 - (4 - isopropoxy - phenyl) - piperidin-1 - yl] - pyrimidin-4 - yl} - amine; (2 - fluoro-4 - methanesulfonyl-- phenyl Yl) - {6 - [4 - (5 - isopropoxy - pyridin-2 - yl) - piperazin-1 - yl] - pyrimidin-4 - yl} - amine; {6 - [4 - (3 - dimethylaminomethyl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl] - pyrimidin-4 - yl} - (2 - fluoro-4 - methanesulfonyl-- phenyl) - amine; ( 2 - fluoro-4 - methane Sulfonyl - phenyl) - (6 - {4 - [2 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - ethyl] - piperazin-1 - yl} - pyrimidin-4 - yl) - amine; (2 - fluoro-4 - methanesulfonyl-- phenyl) - {6 - [4 - (5 - isopropoxy - pyridin-2 - yloxy) - piperidin-1 - yl] - pyrimidin-4 - yl} - amine; (2 - fluoro-4 - methanesulfonyl-- phenyl) - {6 - [4 - (3 - pyridin-3 - yl - [1,2,4] oxadiazol-5 - yl) - piperidin-1 - yl] - pyrimidin-4 - Yl} - amine; 2,5 - difluoro-4 - {6 - [4 - (4 - isopropoxy - phenyl) - piperazin-1 - yl] - pyrimidin-4 - yl amino} - benzoic nitrile; 4 - {[6 - (2 - Fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - ylamino] - methyl} - piperidine-1 - carboxylic acid tert-butyl ester; 4 - {[6 - (2 - fluoro-4 - methyl Alkylsulfonyl - phenylamino) - pyrimidin-4 - ylamino] - methyl} - piperidine-1 - carboxylic acid isopropyl ester; 4 - ({[6 - (2 - fluoro-4 - methanesulfonyl- Yl - phenylamino) - pyrimidin-4 - yl] - isopropyl - amino} - methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ({[4 - (2 - fluoro-4 - CH sulfur Acyl - phenylamino) - pyridin-2 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid isobutyl ester; and 4 - ({[2 - (2 - fluoro-4 - CH Sulfonyl - phenylamino) - pyridin-4 - yl] - methyl - amino} - methyl) - piperidine-1 - carboxylic acid isobutyl ester. ...

International Application No. PCT/US2005/019318 disclosed in the No. Specific examples of GPR119 agonists include the Column according to formula (V) compounds (referred to herein as Group E2): 4 - [6 - (2 - fluoro-4 - methane sulfonyl - phenylamino) - Pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; (2 - fluoro-4 - methanesulfonyl-- phenyl) - {6 - [1 - (3 - isopropyl - [1, 2,4] Oxadiazol-5 - ylmethyl) - piperidin-4 - yloxy] - pyrimidin-4 - yl} - amine; 4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - Pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; (6 - chloro - pyridin-2 - yl) - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenyl ammonia Yl) - pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; (6 - bromo - pyridin-2 - yl) - {4 - [6 - (2 - fluoro-4 - methanesulfonamide acyl - Phenyl Yl) - pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl oxygen Yl] - piperidin-1 - yl} - (6 - methyl - pyridin-2 - yl) - methanone; {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidine -4 - Yloxy] - piperidin-1 - yl} - (6 - fluoro - pyridin-2 - yl) - methanone; {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - Yloxy] - piperidin-1 - yl} - pyridin-2 - yl - methanone; (5 - bromo - pyridin-3 - yl) - {4 - [6 - (2 - fluoro-4 - methanesulfonyl- - Phenyl Yl) - pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yl oxygen Yl] - piperidin-1 - yl} - (5 - methyl - pyridine - 3 - yl) - methanone; (5,6 - Dichloro - pyridin-3 - yl) - {4 - [6 - (2 - fluoro-4 - methanesulfonyl- - Phenylamino) - pyrimidin-4 - yloxy] - piperidin-1 - yl} - methanone; 4 - [6 - (4 - cyano-2 ,5 - difluoro - phenylamino) - pyrimidine -4 - Yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (2,5 - difluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yloxy] - piperidine -1 - carboxylic acid tert-butyl ester; 4 - [6 - (2,4,5 - trifluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (4 - bromo-2 ,5 - difluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (3 - fluoro- -4 - methyl - phenyl Ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (3 - hydroxy - 4 - methoxy - phenyl-amino) - pyrimidin-4 - Yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (6 - cyano - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert- Butyl; 4 - [6 - (3 - chloro-4 - cyano - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (6 - chloro - pyridine -3 - Ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (3 - fluoro-4 - methoxy - phenyl-amino) - pyrimidin-4 - Yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (3,4 - dimethoxy - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid Tert-butyl ester; 4 - [6 - (2,3 - dihydro - benzo [1,4] dioxin-6 - ylamino) - pyrimidin-4 - yloxy] - piperidin- - tert- Butyl; 4 - [6 - (4 - cyano-2 ,5 - difluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - Cyanide -5 - ethyl-amino-2 - fluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (4 - ethoxy-2, 5 - Difluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - ethylthio - phenylamino) - pyrimidine -4 - Yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (4 - isopropyl-thio - phenylamino) - pyrimidin-4 - yloxy] - piperidin- - Carboxylic acid tert-butyl ester; (5 - butyl - pyridin-2 - yl) - {4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyrimidin-4-yloxy] - - Piperidin-1 - yl} - methanone; 4 - [6 - (5 - chloro-3 - methyl - pyridin-2 - yl-amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert- butyl; 4 - [6 - (6 - acetyl-4 - methyl - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - ( 5 - Fluoro-4 - methyl - pyridin-2 - yl-amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (6 - methoxy-5 - methyl- - Pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (6 - methoxy-2 - methyl - pyridine - 3 - yl amino Yl) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (6 - fluoro-5 - methyl - pyridin-3 - ylamino) - pyrimidin-4 - yl oxygen Yl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (2 - chloro-6 - methyl - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - formic acid Tert-butyl ester; 4 - [6 - (4 - methyl - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (2 - methyl - Pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (6 - chloro-2 - methyl - pyridin-3 - ylamino) - Pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (6 - fluoro - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidin- - Carboxylic acid tert-butyl ester; 4 - [6 - (2 - chloro-4 - methyl - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (6 - methoxy - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (5 - fluoro - pyridine -2 - Ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (2 - fluoro - pyridin-3 - ylamino) - pyrimidin-4-yloxy] - - Piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (6 - chloro-5 - methyl - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl Ester; 4 - [6 - (2 - methyl - pyridin-4 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (2 - methoxy- Base - topiramate -3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (2,5 - difluoro - phenylamino) - pyrimidin-4 - yl oxygen Yl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (4 - chloro-2 - fluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester ; 4 - [6 - (2,5 - difluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (6 - methoxy - pyridine -3 - yl Amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - cyano-3 - methoxy - phenyl-amino) - pyrimidin-4 - yloxy Yl] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (3 - fluoro-4 - hydroxy - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl Ester; 4 - [6 - (6 - ethoxy - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2,5- - difluoro-4 - Isopropoxy - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; (2 - fluoro-4 - methanesulfonyl-- phenyl Yl) - [6 - (5'-isopropoxy-3 ,4,5,6 - tetrahydro-2H-[1,2 '] United pyridin-4 - yloxy) - pyrimidin-4 - yl] - amine; (2 - fluoro-4 - methane Sulfonyl - phenyl) - {6 - [1 - (3 - isopropyl - [1,2,4] oxadiazol-5 - yl) - piperidin-4 - yloxy] - pyrimidin-4 - yl} - amine; 4 - [6 - (4 - cyano-2 - fluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (pyridin-3 - yl amino) - Pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (pyridin-4 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isobutyl Propyl; 4 - [6 - (2,5 - difluoro-4 - propoxy - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - Ethyl-amino-2 - fluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - dimethylamino-2 - fluoro - Phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro-4 - propyl-amino - phenylamino) - pyrimidin-4 - Yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro-4 - isopropylamino - phenylamino) - pyrimidin-4 - yloxy] - piperidin- - Isopropyl; 4 - [6 - (2 - methyl-6 - propylamino - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl Ester; 4 - [6 - (2 - methyl - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (6 - isopropyl Ammonia 2 - methyl - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - methyl-6 - propoxy - Pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - iodo-2 - methyl - phenyl-amino) - pyrimidin- -4 - Yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro-4 - iodo - phenylamino) - pyrimidin-4 - yloxy] - piperidin- - formic acid Isopropyl; 4 - {6 - [methyl - (2 - methyl-4 ,5,6,7 - tetrahydro-2H-indazol-3 - yl) - amino] - pyrimidin-4 - yloxy } - piperidine-1 - Isopropyl; 4 - [6 - (2 - methyl-2H-pyrazol-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - phenyl-2H-pyrazol-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (5 - tert- butyl-1H- Pyrazol-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (5 - p-tolyl-1H-pyrazol-3 - yl amino Yl) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (6 - methoxy-5 - methyl - pyridin-3 - ylamino) - pyrimidin-4 - Yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - methyl - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isobutyl Propyl; 4 - [6 - (4 - acetyl-3 - methyl - phenyl-amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - ( 3 - Chloro-4 - fluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (3,5 - dimethoxy - phenylamino) - Pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (6 - ethyl - pyridin-2 - yl-amino) - pyrimidin-4 - yloxy] - piperidine - 1 - carboxylate isopropyl; 4 - [6 - (5 - methyl - pyridin-2 - yl-amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - Methyl - quinolin-6 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - methyl-thio - benzothiazol-6 - Ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (6 - morpholin-4 - yl - pyridin-3 - ylamino) - pyrimidin-4 - Yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - benzenesulfonyl - thiophen-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - Isopropyl; 4 - [6 - (4 - piperidin-1 - yl - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - ( 3 - Trifluoromethoxy-- phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (5 - oxo-5 ,6,7,8 - Four Hydrogen - Naphthalene-2 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (6 - methyl-1H-pyrazolo [3,4-b] pyridin-3 - Ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (5 - cyano - pyridin-2 - yl-amino) - pyrimidin-4 - yloxy Yl] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - bromo-2 ,5 - difluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl Ester; 4 - [6 - (4 - (trifluoromethyl) - pyridin-2 - yl-amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (5 - methyl -1H-pyrazol-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (5 - cyclopropyl-1H-pyrazol-3 - Ammonia Yl) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2,6 - dimethyl - pyridin-3 - ylamino) - pyrimidin-4 - yloxy Yl] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - cyano-2 - methyl - phenyl-amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isobutyl third Ester; 4 - [6 - (4 - methoxy-2 - methyl - phenyl-amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 , 4 - Methoxy - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [Acetyl-- (2 - fluoro-4 - methanesulfonyl- - Phenyl) - amino] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (5 - carbamoyl - pyridin-2 - yl-amino) - Pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [4 - (3,4 - difluoro - phenyl) - thiazol-2 - yl-amino] - pyrimidin-4 - Base Oxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (5 - oxo-1 - phenyl-4 ,5 - dihydro-1H-pyrazol-3 - ylamino) - pyrimidin - 4 - yloxy Yl] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (3 - oxazol-5 - yl - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl Ester; 4 - [6 - (5 - (trifluoromethyl) - pyridin-2 - yl-amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - chloro-2 - Trifluoromethoxy-- phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [(5 - pyridin-2 - yl - thiophene-2 - Ylmethyl) - amino] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [5 - (4 - chloro - phenyl)-2H-pyrazol-3 - Ammonia Yl] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (1 - oxo - indan-5 - ylamino) - pyrimidin-4-yloxy] - - Piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [5 - (1 - methyl - pyrrolidin-2 - yl) - pyridin-2 - yl-amino] - pyrimidin-4 - yloxy} - piperidine pyridine - 1 - carboxylate isopropyl; 4 - [6 - (6 - methoxy-2 - methyl - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl Ester; 4 - [6 - (5 - bromo-3 - methyl - pyridin-2 - yl-amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - ( 2 - chloro -6 - Methyl - pyridin-3 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - ethynyl - phenylamino) - ethyl -4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - bromo - 2 - (Trifluoromethoxy) - phenylamino) - pyrimidin-4-yloxy] - - Piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (3 - iodo-4 - methyl - phenyl-amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro-5 - methyl - phenyl-amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [5 - (4 - methoxy - phenyl Yl) - [1,3,4] thiadiazol-2 - yl-amino] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (3,5 - methyl - Clomazone -4 - ylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [2 - (2,5 - difluoro-4 - propoxy - phenylamino) - Pyridin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2,5 - difluoro-4 - propyl-amino - phenylamino) - pyrimidin-4 - yloxy Yl] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2,5 - difluoro-4 - morpholin-4 - yl - phenylamino) - pyrimidin-4 - yloxy] - piperidine -1 - Isopropyl; 4 - [6 - (2 - methyl - 4 - propyl-amino - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2,5 - difluoro-4 - (4 - methyl - piperazin-1 - yl) - phenylamino] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isobutyl propyl; 4 - {6 - [2,5 - difluoro-4 - (2 - pyrrolidin-1 - yl - ethoxy) - phenylamino] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl Ester; 4 - {6 - [4 - (2 - dimethylamino - ethoxy) -2,5 - difluoro - phenylamino] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl Ester; 4 - {6 - [2,5 - difluoro-4 - (2 - morpholin-4 - yl - ethoxy) - phenylamino] - pyrimidin-4 - yl oxy} - piperidin-1 - Formic acid isopropyl Ester; 4 - [6 - (2,4 - difluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2,4,5 - trifluoromethyl - phenyl Amino) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - methanesulfonyl-- phenylamino) - pyrimidin-4 - yloxy Yl] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [acetyl - (4 - methanesulfonyl - phenyl) - amino] - pyrimidin-4 - yloxy} - piperidine - 1 - carboxylate isopropyl; (2,5 - difluoro-4 - propoxy - phenyl) - {6 - [1 - (5 - isopropyl - [1,2,4] oxadiazol - ³ -) - piperidin-4 - Yloxy] - pyrimidin-4 - yl} - amine; 4 - {6 - [2,5 - difluoro-4 - (morpholin-4 - ylamino) - phenylamino] - pyrimidin-4 - yloxy yl} - piperazine -1 - carboxylic acid isopropyl ester; 4 - {6 - [2,5 - difluoro-4 - (2 - methoxy - ethylamino) - phenylamino] - pyrimidin-4 - yloxy} - piperidine - 1 - carboxylate isopropyl; 4 - (6 - {2,5 - difluoro-4 - [(tetrahydro - furan-2 - ylmethyl) - amino] - phenylamino} - pyrimidin-4 - yl oxygen Yl) - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - butylamino-2 ,5 - difluoro - phenylamino) - pyrimidin-4 - yloxy] - piperidin- - Isopropyl; 4 - {6 - [2,5 - difluoro-4 - (3 - methyl - butylamino) - phenylamino] - pyrimidin-4 - yl oxy} - piperidin-1 - formic acid Isopropyl; 4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenyl-amino) -2 - methyl - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - {6 - [2,5 - difluoro-4 - (2 - morpholin-4 - yl - ethylamino) - phenylamino] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl Ester; 4 - {6 - [2 - (2,5 - difluoro - phenoxy) - ethylamino] - pyrimidin-4 - yloxy} - piperidine-1 - carboxylic acid isopropyl ester; 4 - [ 6 - (2,5 - Difluoro - phenoxy) - pyrimidin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (4 - bromo - 2 - fluoro - phenoxy) - pyrimidin-4 - yloxy Yl] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [6 - (2 - fluoro-4 - morpholin-4 - yl - phenoxy) - pyrimidin-4 - yloxy] - piperidin- - Formic acid Propyl; 4 - {6 - [2,5 - difluoro-4 - (tetrahydro - furan-2 - ylmethoxy) - phenylamino] - pyrimidin-4 - yl oxy} - piperidin-1 - formic acid Isopropyl; 4 - [6 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyridin-2 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - ( 2 - Fluoro-4 - methanesulfonyl-- phenylamino) - pyridin-3 - yloxy] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [6 - (2 - fluoro-4 - methanesulfonyl- Yl - phenylamino) - pyridin-2 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [4 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - Pyridin-2 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester; 4 - [4 - (2,5 - difluoro-4 - propoxy - phenylamino) - pyridin-2 - yloxy ] - Piperidine-1 - carboxylic acid isopropyl ester; and 4 - [2 - (2 - fluoro-4 - methanesulfonyl-- phenylamino) - pyridin-4 - yloxy] - piperidine-1 - carboxylic acid Isopropyl; 4 - [2 - (2,5 - difluoro-4 - propoxy - phenylamino) - pyridin-4 - yloxy] - piperidine-1 - carboxylic acid isopropyl ester. ...

The case description of GPR119 agonist in international application case PCT/GB2004/050046 number (open) with WO2005/061489, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/GB2004/050046 number is formula (VI) chemical compound:

R ¹-A-V-B-R ²

(VI)

Wherein:

V contains maximum 4 heteroatomic 5 yuan of heteroaryl rings that are selected from O, N and S, and it is according to circumstances through C _1-4Alkyl replaces;

A is-CH=CH-or (CH ₂) _n

B is-CH=CH-or (CH ₂) _n, wherein said CH ₂One in the group can be by O, NR ⁵, S (O) _m, C (O) or C (O) NR ¹²Displacement;

N is 0,1,2 or 3 independently;

M is 0,1 or 2 independently;

R ¹Be 3-pyridine radicals or 4-pyridine radicals, 4-pyrimidine radicals or 5-pyrimidine radicals or 2-pyrazinyl, wherein any can replace through one or more substituent groups according to circumstances, and described substituent group is selected from halogen, C _1-4Alkyl, C _1-4Fluoroalkyl, C _2-4Thiazolinyl, C _2-4Alkynyl, C _3-7Cycloalkyl, aryl, OR ⁶, CN, NO ₂, S (O) _mR ⁶, CON (R ⁶) ₂, N (R ⁶) ₂, NR ¹⁰COR ⁶, NR ¹⁰SO ₂R ⁶, SO ₂N (R ⁶) ₂, 4 yuan to 7 yuan of heterocyclic radicals or 5 yuan or 6 yuan of heteroaryls;

R ²Be through R ³, C (O) OR ³, C (O) R ³Or S (O) ₂R ³4 yuan to 7 yuan cycloalkyl that replace; Or containing 4 yuan to 7 yuan heterocyclic radicals of one or two nitrogen-atoms, it is unsubstituted or through C (O) OR ⁴, C (O) R ³, S (O) ₂R ³, C (O) NHR ⁴, P (O) (OR ¹¹) ₂Or 5 yuan or the replacement of 6 membered nitrogen-containing heteroaryl bases;

R ³Be C _3-8Alkyl, C _3-8Thiazolinyl or C _3-8Alkynyl, wherein any can be according to circumstances replaces through maximum 5 fluorine or chlorine atoms, and can contain can be through the metathetical CH of O ₂Group; Or C _3-7Cycloalkyl, aryl, heterocyclic radical, heteroaryl, C _1-4Alkyl C _3-7Cycloalkyl, C _1-4Alkylaryl, C _1-4Alkyl heterocyclic or C _1-4Miscellaneous alkyl aryl, wherein any can replace through one or more substituent groups according to circumstances, and described substituent group is selected from halogen, C _1-4Alkyl, C _1-4Fluoroalkyl, OR ⁶, CN, CO ₂C _1-4Alkyl, N (R ⁶) ₂And NO ₂

R ⁴Be C _2-8Alkyl, C _2-8Thiazolinyl or C _2-8Alkynyl, wherein any can be according to circumstances replaces through maximum 5 fluorine or chlorine atoms, and can contain can be through the metathetical CH of O ₂Group; Or C _3-7Cycloalkyl, aryl, heterocyclic radical, heteroaryl, C _1-4Alkyl C _3-7Cycloalkyl, C _1-4Alkylaryl, C _1-4Alkyl heterocyclic or C _1-4Miscellaneous alkyl aryl, wherein any can replace through one or more substituent groups, and described substituent group is selected from halogen, C _1-4Alkyl, C _1-4Fluoroalkyl, OR ⁶, CN, CO ₂C _1-4Alkyl, N (R ⁶) ₂And NO ₂

R ⁵Be hydrogen, C (O) R ⁷, S (O) ₂R ⁸, according to circumstances through OR ⁶The C that replaces _3-7Cycloalkyl or C _1-4Alkyl, C _3-7Cycloalkyl, aryl, heterocyclic radical or heteroaryl, wherein said cyclic group can replace through one or more substituent groups, and described substituent group is selected from halogen, C _1-2Alkyl, C _1-2Fluoroalkyl, OR ⁶, CN, N (R ⁶) ₂And NO ₂

R ⁶Be hydrogen, C independently _1-4Alkyl, C _3-7Cycloalkyl, aryl, heterocyclic radical or heteroaryl, wherein said cyclic group can replace through one or more substituent groups, and described substituent group is selected from halogen, C _1-4Alkyl, C _1-4Fluoroalkyl, OR ⁹, CN, SO ₂CH ₃, N (R ¹⁰) ₂And NO ₂Or group N (R ¹⁰) ₂Can form and contain another according to circumstances and be selected from O and NR ¹⁰Heteroatomic 4 yuan to 7 yuan heterocycles;

R ⁷Be hydrogen, C _1-4Alkyl, OR ⁶, N (R ⁶) ₂, aryl or heteroaryl;

R ⁸Be C _1-4Alkyl, C _1-4Fluoroalkyl, aryl or heteroaryl;

R ⁹Be hydrogen, C _1-2Alkyl or C _1-2Fluoroalkyl;

R ¹⁰Be hydrogen or C _1-4Alkyl;

R ¹¹It is phenyl; And

R ¹²Be hydrogen, C _1-4Alkyl or C _3-7Cycloalkyl.

International Application No. PCT/GB2004/050046 disclosed in the No. Specific examples of GPR119 agonists include the Column according to formula (VI), the compound (referred to herein as Group F1): 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl methyl Oxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl) piperidine-1 - carboxylic acid tert-butyl ester; 3 - (3 - Pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (4 - pentyl-cyclohexylmethyl) - [1,2,4] Oxadiazol-3 - yl] pyridine; trans-2 - chloro-4 - [5 - (4 - pentyl-cyclohexane) - [1,2,4] oxadiazol-3 - yl] pyridine; anti - 4 - [5 - (4 - E Cyclohexane) - [1,2,4] oxadiazol-3 - yl methyl] pyridine; 4 - (3 - pyridin-4 - yl methyl - [1,2,4] oxadiazol-5 - yl) piperidine-1 - Carboxylic acid tert-butyl ester; trans -3 - [5 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-3 - yl methyl] pyridine; 4 - [5 - (4 - butylcyclohexyl Alkyl) - [1,2,4] oxadiazol-3 - yl] pyridine; 4 - [5 - (4 - n-propyl-cyclohexyl) - [1,2,4] oxadiazol-3 - yl] pyridine; trans-4 - [5 - (4 - Pentylcyclohexane) - [1,2,4] oxadiazol-3 - yl] pyridine; 4 - [2 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl) - ethyl] piperidine - 1 - carboxylate tert-butyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethyl) piperidine-1 - carboxylic acid tert-butyl ester; 3 - [5 - (4 - propyl- Cyclohexyl) - [1,2,4] oxadiazol-3 - yl] pyridine; 3 - [5 - (4 - butyl-cyclohexane) - [1,2,4] oxadiazol-3 - yl] pyridine ; counter -4 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine-2 - carboxylic acid carboxamide; trans-4 - [5 - (4 - pentyl cyclohexane Yl) - [1,2,4] oxadiazol-3 - yl] pyridine-2 - carboxylic acid amide; trans -4 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazole -5 - yl] pyridine Piperidine; trans-2 - chloro-4 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine; trans -3 - [3 - (4 - E cyclohexyl) - [1,2,4] Oxadiazol-5 - yl] pyridine; TRANS-2 - methyl - 3 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine; anti - 2 - chloro -6 - Methyl-4 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine; trans -4 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazole -5 - yl] pyridine-2 - carbonitrile; trans-2 - chloro -3 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine; trans-2 - chloro-6 - Methyl-3 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine; TRANS-2 - methyl-5 - [3 - (4 - E cyclohexyl) - [1,2,4] Oxadiazol-5 - yl] pyridine; trans -3 - methyl -5 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine; anti - 2,6 - dichloro- -4 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine; trans-2 - chloro-6 - methoxy - 4 - [3 - ( 4 - PENTYLCYCLOHEXYL Yl) - [1,2,4] oxadiazol-5 - yl] pyridine; trans-5 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl ] -2 - [1,2,4] triazole -1 - Pyridine; 2 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyrazine; 4 - [3 - (4 - pentyl cyclohexyl ) - [1,2,4] evil Oxadiazol-5 - yl] pyrimidine; trans-5 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine-2 - carbonitrile; trans-5 - chloro-2 - A Thio -4 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyrimidine; trans-2 - fluoro-5 - [3 - (4 - E cyclohexyl) - [1,2,4] Oxadiazol-5 - yl] pyridine; trans-2 - fluoro-4 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine; TRANS- - imidazol-1 - -5 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine; TRANS-2 - methyl - 4 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] Oxadiazol-5 - yl] pyridine; trans-3 - methyl - 4 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] pyridine; counter -4 - {2 - [3 - (4 - pentyl cyclohexyl) - [1,2,4] oxadiazol-5 - yl] vinyl} pyridine; 4 - (5 - pyridin-4 - yl - [ 1,2,4] oxadiazole -3 - Ylmethoxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (2 - cyano-4 - yl) - [1,2,4] oxadiazol-3 - yl methyl oxy] piperidine - 1 - carboxylate tert-butyl ester; (E) -4 - [5 - (2 - pyridin-3 - yl - vinyl) - [1,2,4] oxadiazol-3 - ylmethoxy]-piperidine - 1 - carboxylate tert- Dioxide; (E) -4 - [5 - (2 - pyridin-3 - yl - vinyl) - [1,2,4] oxadiazol-3 - yl] piperidine-1 - carboxylic acid tert-butyl ester; (E) -4 - [5 - (2 - Pyridin-3 - yl - vinyl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid tert-butyl ester; (E) -4 - [5 - (2 - pyridyl -4 - yl - B Enyl) - [1,2,4] oxadiazol-3 - yl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (2 - pyridin-4 - yl - ethyl) - [1, 2,4] oxadiazol-3 - Yl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - {5 - [2 - (2 - cyano-4 - yl) ethyl] - [1,2,4] oxadiazol-3 - yl } piperidine-1 - carboxylic acid Tert-butyl ester; 4 - {5 - [2 - (2 - cyano-4 - yl) ethyl] - [1,2,4] oxadiazol-3 - ylmethoxy} piperidine-1 - carboxylic acid tert-butyl ester; 4 - {5 - [2 - (2 - cyano-4 - yl) ethyl] - [1,2,4] oxadiazol-3 - yl methyl} piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - piperidine -4 - Yl - [1,2,4] oxadiazol-3 - yl) pyridine; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl) piperidine - 1 - carboxylate isobutyl; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl) piperidine-1 - acid 2 - methoxy-ethyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazole -5 - yl) piperidine-1 - carboxylate; 3,3 - dimethyl-1 - [4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl) piperidin-1 - yl] Butan-1 - one China; - cyclopentyl-1 - [4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl) piperidin-1 - yl] ethanone ; 4 - {5 - [1 - (butane-1 - Sulfonyl)-piperidin-4 - yl] - [1,2,4] oxadiazol-3 - yl}-pyridine; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol - 5 - yl) piperidine-1 - Acid propanamide; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl) piperidine-1 - carboxylic acid tert-butylamide; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid cyclopentyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazole -5 - ylmethoxy) Piperidine-1 - carboxylic acid benzyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid isobutyl ester; 4 - (3 - Pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid ethyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4 ] oxadiazol-5 - Ylmethoxy) piperidine-1 - carboxylic acid cycloheptyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid armor Ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - acid 2 - methoxy - ester; 4 - (3 - pyridin - Yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid isopropyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazole -5 - ylmethoxy Yl) piperidine-1 - acid 4 - methoxy - phenyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - formic acid 2,2,2 - trichloroethyl; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - acid 4 - chloro - phenyl ester; 4 - (3 - Pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid phenyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4 ] oxadiazol-5 - Ylmethoxy) piperidine-1 - acid 2 - ethyl - hexyl acrylate; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine -1 - A Propyl gallate; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid hexyl ester; 4 - (3 - pyridin- - Base - [1,2,4] Oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid (1R, 2S, 5R) -2 - isopropyl-5 - methyl-cyclohexyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid (1S, 2R, 5S) -2 - isopropyl-5 - methyl-cyclohexyl ester; 4 - ( 3 - pyridin - Yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid 2,2 - dimethyl-propyl; 4 - (3 - pyridin-4 - yl - [1, 2,4] oxadiazole -5 - Ylmethoxy) piperidine-1 - carboxylic acid naphthalen-1 - yl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidin-1 - A Acid, 2 - methoxy - phenyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - acid 3 - trifluoromethyl benzene Ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid prop-2 - ynyl ester; 4 - (3 - pyridine-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylate butan-2 - ynyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4 ] oxadiazol-5 - yl methyl Oxy) piperidine-1 - carboxylic acid pentyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid p-tolyl ester ; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - acid 2 - chloro - phenyl ester; 4 - (3 - pyridin- - Base - [1,2,4] Oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid-2 - yl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl methyl oxy) piperidine -1 - carboxylic acid butyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - acid 4 - methoxycarbonyl - benzene esters; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - acid 4 - fluoro - phenyl ester; 3 - methyl-1 - [ 4 - (3 - pyridin - Yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidin-1 - yl] - butan-1 - one; phenyl - [4 - (3 - pyridin-4 - yl - [ 1,2,4] oxadiazol-5 - Ylmethoxy) piperidin-1 - yl] methanone; 1 - [4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine - 1 - yl] butan-1 - One; 2,2 - dimethyl-1 - [4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidin-1 - yl] propyl -1 - one; cyclopentyl - [4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidin-1 - yl] methanone; [4 - (3 - pyridin- - Base - [1,2,4] oxadiazole -5 - ylmethoxy) piperidin-1 - yl] - p-tolyl ketone; 3,3 - dimethyl-1 - [4 - (3 - pyridin-4 - yl - [1,2, 4] oxadiazol-5 - Ylmethoxy) piperidin-1 - yl] butan-1 - one; 4 - {5 - [1 - (butane-1 - sulfonyl)-piperidin-4 - yloxy methyl] - [1, 2,4] oxadiazole -3 - Yl}-pyridine; 4 - {5 - [1 - (propane-1 - sulfonyl)-piperidin-4 - yloxy methyl] - [1,2,4] oxadiazol-3 - yl} pyridine; 4 - (3 - Pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid tert-butylamide; 4 - (3 - pyridin-4 - yl - [1,2, 4] oxadiazole -5 - Ylmethoxy) piperidine-1 - carboxylic acid amide o-tolyl; trans -4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl) cyclohexane armor Propyl gallate; trans -4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl) cyclohexane carboxylic acid ester; trans -4 - (3 - pyridin - Base - [1,2,4] Oxadiazol-5 - yl) cyclohexanecarboxylic acid isobutyl ester; trans-4 - [5 - (4 - propoxy-methyl-cyclohexyl) - [1,2,4] oxadiazol-3 - yl] topiramate Piperidine; trans-4 - [5 - (4 - methyl-cyclohexyl-butoxy) - [1,2,4] oxadiazol-3 - yl] pyridine; cis -4 - [5 - (3 - butoxy methyl cyclopentyl Yl) - [1,2,4] oxadiazol-3 - yl] pyridine; cis -4 - [5 - (3 - methyl-propoxy-cyclopentyl) - [1,2,4] oxadiazole -3 - yl] pyridine; cis -4 - [5 - (3 - butoxy-methyl-cyclohexyl) - [1,2,4] oxadiazol-3 - yl] pyridine; 4 - (3 - pyridin-4 - yl - [1,2 , 4] oxadiazol-5 - yl Methoxy) -3,4,5,6 - tetrahydro-2H-[1,3 '] bipyridine; 2 - [4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazole -5 - ylmethoxy) piperidine -1 - Yl] pyrazine; 2 - [4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidin-1 - yl] pyrimidine; ( 4 - PENTYLCYCLOHEXYL Yl) - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethyl) amine; (4 - pentyl cyclohexyl - methyl) - (3 - pyridin - Base - [1,2,4] Oxadiazol-5 - ylmethyl) amine; 4 - [(3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl methyl) amino] piperidine-1 - carboxylic acid tert- butyl; 4 - {[3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl methyl) amino] methyl} - piperidine-1 - carboxylic acid tert-butyl ester; 4 - {[5 - (2 - cyano-pyridine -4 - yl) - [1,2,4] oxadiazol-3 - yl methyl] amino} - piperidine-1 - carboxylic acid tert-butyl ester; methyl - (4 - pentyl cyclohexyl) - ( 3 - topiramate -4 - yl - [1,2,4] oxadiazol-5 - ylmethyl) amine; methyl - (4 - methyl-pentyl cyclohexyl) - (3 - pyridin-4 - yl - [1 , 2,4] oxadiazole -5 - Ylmethyl) amine; 4 - [methyl - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl methyl) amino] piperidine-1 - carboxylic acid tert- butyl; 4 - [ethyl - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl methyl) amino] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [propyl - (3 - pyridyl -4 - Yl - [1,2,4] oxadiazol-5 - yl methyl) amino] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [cyclopropylmethyl - (3 - pyridin - base - [1,2,4] oxadiazol-5 - yl methyl) amino] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [butyl - (3 - pyridin-4 - yl - [1,2, 4] oxadiazol-5 - Ylmethyl) amino] piperidine-1 - carboxylic acid tert-butyl ester; 4 - {[methyl - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl methyl) amino ] Methyl} - piperidine-1 - carboxylic acid tert-butyl ester; 4 - {[ethyl - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl methyl) amino] methyl yl} - Piperidine-1 - carboxylic acid tert-butyl ester; 4 - {[5 - (2 - cyano-4 - yl) - [1,2,4] oxadiazol-3 - ylmethyl]-ethylamino} - piperidin-1 - Carboxylic acid tert-butyl ester; 4 - [methyl - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl methyl) amino] piperidine-1 - carboxylic acid cyclopentyl ester; 4 - {[methyl - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl methyl) amino] methyl} - piperidine-1 - carboxylic acid 2,2,2 - Trichloroethyl; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - methyl-ylmethoxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridin - Base - [1,2,4] Oxadiazol-5 - ylmethyl) piperazine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - yl methyl group) piperidine - 1 - carboxylate tert-butyl ester; 4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - methanesulfonyl-yl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - ( 5 - Pyridin-4 - yl - [1,3,4] oxadiazol-2 - ylmethoxy) piperidine-1 - carboxylic acid tert-butyl ester; 3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - Acid (4 - pentylcyclohexyl) amide; [4 - (3 - pyridin-4 - yl - [1,2,4] oxadiazol-5 - ylmethoxy) piperidin-1 - yl] phosphonic acid diphenyl Ester; 4 - (4 - pyridin-4 - yl - thiazol-2 - ylmethoxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - pyridin-4 - yl - thiazol-4 - yl methyl ) Piperidine-1 - carboxylic acid tert-butyl ester; trans-4 - [5 - (4 - pentyl - cyclohexyl) - [1,3,4] thiadiazol-2 - yl] pyridine; 4 - (5 - pyridin- -4 - yl - [1,3,4] thiadiazol-2 - ylmethoxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - pyridin-4 - yl-4H-[1,2,4] three zol-3 - ylmethoxy Yl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (5 - pyridin-4 - yl - isoxazol-3 - yl) ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - ( 5 - Pyridin-4 - yl - isoxazol-3 - ylmethoxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - pyridin-4 - yl - isoxazol-3 - yl) piperidin- - 1 - carboxylate tert-butyl ester; 4 - [2 - (1 - methyl -5 - pyridin-4 - yl-1H-pyrazol-3 - yl) ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (2 - methyl-5 - pyridin-4 - yl-2H-pyrazol-3 - yl) ethyl] - piperidine-1 - carboxylic acid tert-butyl ester; (E) -4 - {5 - [2 - (2 - cyano-pyridine -4 - yl) ethenyl] - [1,2,4] oxadiazol-3 - yl} piperidine-1 - carboxylic acid tert-butyl ester; 4 - {5 - [2 - (2H-tetrazol-5 - yl) pyridin - Yl] - [1,2,4] oxadiazol-3 - ylmethoxy} - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (2 - cyano-4 - yl) - [ 1,2,4] oxadiazole -3 - Ylmethoxy] piperidine-1 - carboxylic acid isopropyl ester; and 4 - [5 - (2 - cyano-4 - yl) - [1,2,4] oxadiazol-3 - yl methoxy] Piperidine-1 - carboxylic acid benzyl ester. ...

The case description of GPR119 agonist in international application case PCT/US06/00567 number (open) with WO 2006/083491, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/US06/00567 number is formula (VII) chemical compound:

Wherein:

X is N or CR ₈, R wherein ₈Be H or halogen;

Y is NH or O;

Z is CH or N;

R ₁Be C _1-6Alkoxy carbonyl group, oxadiazole base or pyrimidine radicals, wherein said C _1-6Alkoxy carbonyl group, oxadiazole base and pyrimidine radicals replace through 1 or 2 substituent group separately according to circumstances, and described substituent group is independently selected from by C _1-4Alkyl, C _1-4Alkoxyl and C _3-5The group that cycloalkyl is formed;

R ₂Be H or C _1-4Alkyl;

R ₃Be C _1-4Alkoxyl, O-C _2-4-alkynyl or hydroxyl;

R ₄Be selected from by H, C _1-4Alkoxyl, C _1-4Alkyl, C _2-4The group that alkynyl and halogen are formed;

R ₅Be selected from by C _1-4Acyl group sulfonamide, C _1-4Alkoxyl, C _1-4Alkyl, C _1-4Alkyl amino, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, cyano group, heterocyclic radical, two-C _1-4The group that dialkyl amido and sulfonamide are formed, wherein said C _1-4Alkoxyl, C _1-4Alkyl, C _1-4Alkyl amino, C _1-4Alkyl sulphonyl, C _1-4Alkyl sulfenyl, two-C _1-4Dialkyl amido and heterocyclic radical replace through 1 or 2 substituent group separately according to circumstances, and described substituent group is independently selected from by C _2-4Alkynyl, C _1-4Alkoxyl, C _1-4Alkyl formamides, C _1-4Alkyl sulphonyl, C _3-5Cycloalkyl, C _3-5Cycloalkyl oxy, two C _1-4The group that alkyl formamides, hydroxyl and phosphonato are formed, wherein said C _1-4Alkyl formamides replaces through hydroxyl according to circumstances; Or

R ₅Be the group of formula (VIIA):

Wherein " m ", " n " and " q " are 0,1,2 or 3 independently of one another; " r " is 0,1 or 2; And " t " is 0 or 1;

R ₆Be H or halogen; And

R ₇Be H or C _1-4Alkyl.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US06/00567 number comprises following chemical compound according to formula (VII) (being referred to herein as the G1 group): 4-[6-(4-methane sulfonyl-2-methoxyl group-phenyl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{5-methoxyl group-6-[6-(2-methoxyl group-ethyl)-2-methyl-pyridin-3-yl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2-methane sulfonyl-ethyl)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-formic acid 1-cyclopropyl-ethyl ester; 4-[6-(2-fluoro-4-methane sulfonyl-phenyl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(4-cyano group-2-fluoro-phenyl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{6-[6-(2-hydroxyl-ethyl)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2-methane sulfonyl-ethyl)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{5-methoxyl group-6-[6-(2-methoxyl group-ethylamino)-2-methyl-pyridin-3-yl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2-methane sulfonyl-ethyoxyl)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2-hydroxyl-propyl group amino)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(3-hydroxyl-propyl group)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{5-methoxyl group-6-[2-methyl-6-(3-phosphonato-propyl group)-pyridin-3-yl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2-methane sulfonyl-ethylamino)-2-methoxyl group-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2-methane sulfonyl-propyl group amino)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[6-(6-formyl-dimethylamino methyl-2-methyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-(6-{2-fluoro-4-[(2-hydroxyl-ethylamino formoxyl)-methyl]-phenyl amino }-5-methoxyl group-pyrimidine-4-base oxygen base)-piperidines-1-isopropyl formate; 4-{6-[6-(2-methane sulfonyl-ethylamino)-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[2-fluoro-4-(2-hydroxyl-ethyl sulfenyl)-phenyl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2,3-dihydroxy-propyl group amino)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2,3-dihydroxy-propyl group amino)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2-hydroxyl-ethyoxyl)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{5-methoxyl group-6-[2-methyl-6-(2-phosphonato-ethyoxyl)-pyridin-3-yl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(3-hydroxyl-propoxyl group)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; With 4-{5-methoxyl group-6-[2-methyl-6-(3-phosphonato-propoxyl group)-pyridin-3-yl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US06/00567 number comprises following chemical compound according to formula (VII) (being referred to herein as the G2 group): 4-[2-(2-fluoro-4-propoxyl group-phenyl amino)-3-methoxyl group-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-{2-[2-fluoro-4-(2-hydroxyl-ethyl)-phenyl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-[5-fluoro-2-(2-fluoro-4-methane sulfonyl-phenyl amino)-3-methoxyl group-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-{2-[2-ethyl-4-(2-methane sulfonyl-ethyl)-phenyl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-2-methyl-piperidines-1-isopropyl formate; 4-{5-fluoro-2-[6-(2-hydroxyl-ethyoxyl)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[2-fluoro-4-(2-methane sulfonyl-ethyl)-phenyl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[6-(2-hydroxyl-ethylamino)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-[2-(4-cyano group-2-fluoro-phenyl amino)-3-methoxyl group-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-[2-(2-chloro-4-cyano group-phenyl amino)-3-methoxyl group-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-{2-[6-(2-methane sulfonyl-ethyl)-2-methoxyl group-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[6-(2-methane sulfonyl-ethyl)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[6-(2-hydroxyl-ethyl)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[6-(3-hydroxyl-butyl)-2-methoxyl group-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[2-fluoro-4-(2-hydroxyl-ethyoxyl)-phenyl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{3-ethyoxyl-2-[2-fluoro-4-(2-phosphonato-ethyl)-phenyl amino]-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-[3-methoxyl group-2-(2-methoxyl group-4-propiono sulfamoyl-phenyl amino)-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-[2-(2,5-two fluoro-4-propoxyl group-phenyl aminos)-3-methoxyl group-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; (2-fluoro-4-methane sulfonyl-phenyl)-4-[1-(the 5-isopropyl-[1,2,4] oxadiazole-3-yls)-piperidin-4-yl oxygen base]-3-methoxyl group-pyridine-2-yl }-amine; (2-fluoro-4-methane sulfonyl-phenyl)-3-methoxyl group-4-[1-(5-methoxyl group-pyrimidine-2-base)-piperidin-4-yl oxygen base]-pyridine-2-yl }-amine; 4-{2-[6-(2-encircles propoxyl group-ethyl)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-[2-(2-chloro-4-methane sulfonyl-phenyl amino)-5-fluoro-3-methoxyl group-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-[3-ethyoxyl-2-(4-methane sulfonyl-2-methoxyl group-phenyl amino)-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-[2-(5-fluoro-2-methyl-4-propoxyl group-phenyl amino)-3-methoxyl group-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-{2-[6-(2-methane sulfonyl-ethyl)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-[2-(2-fluoro-4-methane sulfonyl-phenyl amino)-3-hydroxyl-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-[2-(2-chloro-4-propoxyl group-phenyl amino)-3-methoxyl group-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-{3-methoxyl group-2-[2-methyl-6-(2-phosphonato-ethyl)-pyridin-3-yl amino]-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[6-(2-methane sulfonyl-ethylamino)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-(2-{6-[(2-methane sulfonyl-ethyl)-methyl-amino]-2-methyl-pyridin-3-yl amino }-3-methoxyl group-pyridin-4-yl oxygen base)-piperidines-1-isopropyl formate; 4-{2-[6-(3-methane sulfonyl-pyrrolidine-1-yl)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-[2-(3-methane sulfonyl-6 '-methyl-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-5 '-Ji amino)-3-methoxyl group-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-{2-[6-(3-methane sulfonyl-azetidine-1-yl)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-[3-acetenyl oxygen base-2-(2-fluoro-4-methane sulfonyl-phenyl amino)-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-{2-[2-fluoro-4-(2-phosphonato-ethane sulfonyl)-phenyl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-[2-(4-ethane sulfonyl-2-fluoro-phenyl amino)-3-methoxyl group-pyridin-4-yl oxygen base]-piperidines-1-sec.-butyl formate; 4-{2-[6-(2,3-dihydroxy-propyl group amino)-4-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[6-(2-hydroxyl-ethyl sulfenyl)-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[2-fluoro-4-(2-hydroxyl-ethane sulfonyl)-phenyl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[6-(2-hydroxyl-ethyoxyl)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{3-methoxyl group-2-[2-methyl-6-(2-phosphonato-ethyoxyl)-pyridin-3-yl amino]-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[6-(3-hydroxyl-propoxyl group)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{3-methoxyl group-2-[2-methyl-6-(3-phosphonato-propoxyl group)-pyridin-3-yl amino]-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-[3-methoxyl group-2-(2-methoxyl group-4-sulfamoyl-phenyl amino)-pyridin-4-yl oxygen base]-piperidines-1-isopropyl formate; 4-{2-[2-fluoro-4-(3-phosphonato-propyl group)-phenyl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[6-(2-hydroxyl-ethyl)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{3-methoxyl group-2-[2-methyl-6-(2-phosphonato-ethyl)-pyridin-3-yl amino]-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; 4-{2-[6-(3-hydroxyl-propyl group)-2-methyl-pyridin-3-yl amino]-3-methoxyl group-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate; With 4-{3-methoxyl group-2-[2-methyl-6-(3-phosphonato-propyl group)-pyridin-3-yl amino]-pyridin-4-yl oxygen base }-piperidines-1-isopropyl formate.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/US06/00567 number comprises following chemical compound according to formula (VII) (being referred to herein as the G3 group): 4-[6-(2,6-dimethyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(6-methane sulfonyl-2-methyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(6-methane sulfonyl-4-methyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-methoxyl group-6-(2-methyl-6-propyl group sulfenyl-pyridin-3-yl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{5-methoxyl group-6-[2-methyl-6-(propane-1-sulfonyl)-pyridin-3-yl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[6-(6-ethyl sulfenyl-2-methyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(6-ethane sulfonyl-2-methyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(6-isopropyl sulfenyl-2-methyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-{5-methoxyl group-6-[2-methyl-6-(third-2-sulfonyl)-pyridin-3-yl amino]-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-{6-[6-(2-hydroxyl-ethane sulfonyl)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-isopropyl formate; 4-[5-hydroxyl-6-(6-methane sulfonyl-2-methyl-pyridin-3-yl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-ethyoxyl-6-(6-methane sulfonyl-2-methyl-pyridin-3-yl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[5-isopropoxy-6-(6-methane sulfonyl-2-methyl-pyridin-3-yl amino)-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(6-methane sulfonyl-2-methyl-pyridin-3-yl amino)-5-propoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(6-methane sulfonyl-2-methyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-formic acid 1-ethyl-propyl ester; 4-[6-(6-methane sulfonyl-2-methyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-sec.-butyl formate; 4-[6-(6-cyano group-4-methyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 4-[6-(6-hydroxymethyl-4-methyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; 6-[1-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidin-4-yl oxygen base]-5-methoxyl group-pyrimidine-4-yl }-(6-methane sulfonyl-2-methyl-pyridin-3-yl)-amine; 4-[6-(6-methane sulfonyl-2,4-dimethyl-pyridin-3-yl amino)-5-methoxyl group-pyrimidine-4-base oxygen base]-piperidines-1-isopropyl formate; And 4-{6-[6-(1-methane sulfonyl-1-methyl-ethyl)-2-methyl-pyridin-3-yl amino]-5-methoxyl group-pyrimidine-4-base oxygen base }-piperidines-1-formic acid isopropyl.

The case description of GPR119 agonist in international application case PCT/GB2005/050264 number (open) with WO2006/067531, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/GB2005/050264 number is formula (VIII) chemical compound:

Wherein:

Among A and the B one is that nitrogen and another are CR ¹

W and Y are key, unbranched or side chain C independently _1-3Alkylidene or unbranched or side chain C _2-3Alkenylene;

X is selected from CH ₂, O, S, CH (OH), CH (halogen), C (O), C (O) O, C (O) S, SC (O), C (O) CH ₂S, C (O) CH ₂C (OH), C (O) CH ₂C (O), OC (O), NR ⁵, CH (NR ⁵R ⁵⁵), C (O) NR ², S (O) and S (O) ₂

G is CHR ³, N-C (O) OR ⁴, N-C (O) NR ⁴R ⁵, N-C _1-4Alkylidene-C (O) OR ⁴, N-C (O) C (O) OR ⁴, N-S (O) ₂R ⁴, N-C (O) R ⁴Or N-P (O) (O-Ph) ₂Or N-heterocyclic radical or N-heteroaryl, wherein any can replace through one or two group according to circumstances, and described group is selected from C _1-4Alkyl, C _1-4Alkoxy or halogen;

R ¹Be hydrogen, halogen, cyano group, C (O) NH ₂, C _1-4Alkyl, SO ₂C _1-4Alkyl, SOC _1-4Alkyl or SC _1-4Alkyl;

R ²Be hydrogen or C _1-4Alkyl;

R ³Be C _3-6Alkyl;

R ⁴Be C _1-8Alkyl, C _2-8Thiazolinyl or C _2-8Alkynyl, wherein any can be according to circumstances through one or more halogen atoms, NR ⁵R ⁵⁵, OR ⁵, C (O) OR ⁵, OC (O) R ⁵Or cyano group replaces, and can contain can be through O or the metathetical CH of S ₂Group; Or C _3-7Cycloalkyl, aryl, heterocyclic radical, heteroaryl, C _1-4Alkylidene C _3-7Cycloalkyl, C _1-4Alkylidene aryl, C _1-4Alkylene heterocyclic base or C _1-4The alkylidene heteroaryl, wherein any can replace through one or more substituent groups, and described substituent group is selected from halogen, C _1-4Alkyl, C _1-4Fluoroalkyl, OR ⁵, CN, NR ⁵R ⁵⁵, SO ₂Me, NO ₂Or C (O) OR ⁵

R ⁵And R ⁵⁵Be hydrogen or C independently _1-4Alkyl; Or R ⁵And R ⁵⁵Connect together and to form 5 yuan or 6 yuan of heterocycles;

R ⁶Be hydrogen, halogen, CN, C _1-4Alkyl, C _1-4Alkoxyl, acetenyl, C (O) NR ⁷R ⁷⁷Or C _1-4Alkylidene S (O) _f

R ⁷And R ⁷⁷Be hydrogen or C independently _1-4Alkyl; Or R ⁷And R ⁷⁷Connect together and to form 5 yuan or 6 yuan of heterocycles;

R ⁸Be hydrogen, halogen, CN, C _1-4Alkyl or C _1-4Alkoxyl;

R ¹¹Be hydrogen or hydroxyl;

D is 0,1,2 or 3;

E is 1,2,3,4 or 5;

Condition is that d+e is 2,3,4 or 5; And

F is 0,1 or 2.

International Application No. PCT/GB2005/050264 disclosed in the No. Specific examples of GPR119 agonists include the Column according to formula (VIII) of the compound (referred to herein as Group H1): 4 - (3 - pyridin-4 - yl-propyl thio-carbonyl) piperidine - 1 - carboxylate tert-butyl ester; 4 - pentylcyclohexane thiocarbonate S-(3 - pyridin-4 - yl-propyl) ester; 4 - (2 - pyridin-4 - yl-ethyl group Carbonyl)-piperidine-1 - carboxylic acid tert-butyl ester; 4 - pentylcyclohexane thiocarbonate S-(2 - pyridin-4 - yl-ethyl) ester; 4 - (pyridin-4 - carbonyl Ylthio) piperidine-1 - carboxylic acid tert-butyl ester; (E) -4 - (3 - pyridin-4 - yl acryloyl group) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - Pyridin-4 - yl group propionyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (pyridin-4 - methyl thio carbonyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridin-4 - methyl-propionyl group) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - pyridin-4 - yl acetoxymethyl) piperidine - 1 - carboxylate tert-butyl ester; 4 - (2 - pyridin-4 - acetoxy-yl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [3 - (2 - pyridin-4 - yl acetoxy) Propyl] piperidine-1 - carboxylic acid tert-butyl ester; isonicotinic acid 3 - (1 - tert-butoxycarbonyl-piperidin-4 - yl) propyl; (E) -4 - (3 - pyridin-4 - yl C Enoyl methyl) piperidine-1 - carboxylic acid tert-butyl ester; (E) -4 - (3 - pyridin-4 - yl acryloyl oxy) piperidine-1 - carboxylic acid tert-butyl Esters; (E) -4 - [3 - (3 - pyridin-4 - yl acryloyl oxy) propyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - pyridin-4 - yl ethoxycarbonyl Ylmethyl) piperidine-1 - carboxylic acid tert-butyl ester; piperidine-1 ,4 - dicarboxylic acid 1 - tert-butyl 4 - (2 - pyridin-4 - yl-ethyl) ester; piperidine-1 ,4 - Dicarboxylic acid 1 - tert-butyl 4 - (3 - pyridin-4 - yl-propyl) ester; (E) -4 - [methyl-(3 - pyridin-4 - yl acryloyl)-amino] piperidine-1 - Carboxylic acid tert-butyl ester; 4 - {2 - [methyl-(pyridine-4 - carbonyl) amino] ethyl} piperidine-1 - carboxylic acid tert-butyl ester; 4 - [methyl-(pyridin-4 - Carbonyl) amino] piperidine-1 - carboxylic acid tert-butyl ester; 4 - {2 - [methyl-(2 - pyridin-4 - yl) amino] ethyl} piperidine-1 - carboxylic acid tert- Butyl; 4 - {2 - [methyl-(3 - pyridin-4 - yl acryloyl)-amino] ethyl} piperidine-1 - carboxylic acid tert-butyl ester; 4 - {[methyl - (3 - pyridine -4 - yl acryloyl) amino] methyl} piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - pyridin-4 - yl-ethyl thio methyl) piperidine-1 - Carboxylic acid tert-butyl ester; 4 - (2 - pyridin-4 - yl-ethyl thio) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (2 - pyridin-4 - yl-ethyl group) Ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridin-4 - yl-propyl thio methyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridin - Propyl thio) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (3 - pyridin-4 - yl-propyl thio) ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - pyridin-4 - yl-ethoxy methyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridin-4 - yl-propoxy methyl) piperidine-1 - carboxylic acid Tert-butyl ester; 4 - [2 - (3 - pyridin-4 - yl-propoxy) ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (2 - pyridin-4 - yl-ethoxy ) B Yl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [3 - (2 - cyano-4 - yl) propoxy methyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - {2 - [3 - (2 - cyano-4 - yl) propoxy] ethyl} piperidine-1 - carboxylic acid tert-butyl ester; 4 - [3 - pyridin-4 - methoxy C yl] Piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (2 - bromo-4 - yl) ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridin - Yl-propoxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [3 - (pyridin-4 - yl) propyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (pyridin- -4 - Yl) ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - oxo-2 - pyridin-4 - yl-ethyl thio methyl) piperidine-1 - carboxylic acid Tert-butyl ester; 4 - (3 - pyridin-4 - yl propane-1 - sulfonyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridin-4 - yl-propan-1 - sulfinyl Yl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridin-4 - yl propane-1 - sulfonyl methyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridine -4 - yl-propan-1 - sulfinyl-ylmethyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (3 - pyridin-4 - yl propane-1 - sulfonyl) ethyl] Piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (3 - pyridin-4 - yl-propan-1 - sulfinyl) ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - Pyridin-4 - yl ethane sulfonyl methyl) piperidine-1 - carboxylic acid tert-butyl ester; (E) -4 - (2 - oxo-4 - pyridin-4 - butyric -3 - enyl) piperidine - 1 - carboxylate tert-butyl ester; (E) -4 - (4 - pyridin-4 - butyric -3 - enyl) piperidine-1 - carboxylic acid tert-butyl ester; (Z) -4 - (4 - pyridin - 4 - butyric -3 - Enyl)-piperidine-1 - carboxylic acid tert-butyl ester; (E) -4 - (3 - pyridin-4 - allyl) piperidine-1 - carboxylic acid tert-butyl ester; (Z) -4 - (3 - pyridin-4 - Allyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - pyridin-4 - yl Propyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - methyl - 3 - pyridin-4 - yl-propyl) piperidine-1 - carboxylic acid tert-butyl ester; (E) -4 - [4 - (2 - Cyano-4 - yl) but-3 - enyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [4 - (2 - cyano-4 - yl) butyl] piperidine-1 - carboxylic acid Tert-butyl ester; 4 - [3 - (2 - cyano-4 - yl) propyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (2 - cyano-4 - ylmethoxy yl) Ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert-butylamide; 4 - (4 - pyridin - butyric Yl) piperidine-1 - carboxylic acid tert-butyl carboxamide; 4 - (4 - pyridin-4 - yl - butyl) piperidine-1 - carboxylic acid 2,2,2 - trichloroethyl ester; 4 - (4 - -4 - butyl) piperidine-1 - carboxylic acid isobutyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - acid 4 - methoxy-phenyl ester; 4 - (4 - -4 - butyl) piperidine-1 - carboxylic acid 2,2 - dimethyl-propyl; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid phenyl ester; 4 - (4 - -4 - butyl) piperidine-1 - carboxylic acid cyclopentyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - acid 2 - chloro-benzyl ester; 4 - (4 - pyridine -4 - butyl) piperidine-1 - carboxylic acid p-tolyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid ester; 4 - (4 - pyridin - Butyl) piperidine-1 - carboxylic acid hexyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid prop-2 - propargyl ester; 4 - (4 - pyridin - butyric Yl) piperidine-1 - carboxylic acid naphthalen-1 - yl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - acid 4 - fluorophenyl ester; 4 - (4 - pyridin-4 - yl Ding Yl) piperidine-1 - acid 4 - methoxycarbonyl-phenyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid 4 - nitrophenyl ester; 4 - (4 - pyridine -4 - butyl) piperidine-1 - carboxylic acid isopropyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - acid 4 - chlorophenyl ester; 4 - (4 - pyridyl - 4 - Butyl) piperidine-1 - acid 3 - (trifluoromethyl) phenyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - acid 2 - chlorophenyl; 4 - (4 - -4 - butyl) piperidine-1 - acid 2 - methoxy-phenyl ester; 4 - (4 - pyridin-4 - yl - butyl) piperidine-1 - carboxylic acid but-2 - alkynyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid-2 - yl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid pentyl ester; 4 - (4 - -4 - butyl) piperidine-1 - carboxylic acid o-tolyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - acid 2 - cyano-1 ,1 - dimethyl Yl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid 2,2,2 - trifluoroethyl ester; 4 - (4 - pyridin-4 - butyl) piperidine - 1 - Butyl formate ring; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid cyclohexyl ester; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid 2 - methyl group, ethyl; 4 - (4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tetrahydrofuran-2 - yl ester; 2 - [4 - (4 - pyridin - Methylbutyl) piperidin-1 - yl] propanoate; [4 - (4 - pyridin-4 - butyl) piperidin-1 - yl] acetate; [4 - (4 - pyridin- - Base Butyl)-piperidin-1 - yl] acetic acid tert-butyl ester; Oxo - [4 - (4 - pyridin-4 - butyl) piperidin-1 - yl] acetate; 2 - [4 - (4 - topiramate -4 - butyl) piperidin-1 - yl] pyrimidine; 4 - (4 - pyridin-4 - butyl) -3,4,5,6 - tetrahydro-2H-[1,2 '] bipyridine; 4 - (2,4 - Dioxo-4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3,5 - dioxo-5 - pyridin-4 - yl - pentyl) piperidine - A Acid tert-butyl ester; 4 - [1 - (2 - cyano-4 - yl) ethenyl methyl carbonyl oxy] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - hydroxy - 4 - -4 - butyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - hydroxy - 4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - Hydroxy-4 - oxo-4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [4 - (2 - cyano-4 - yl) - 2 - hydroxy - 4 - oxo Butyl]-piperidine-1 - carboxylic acid tert-butyl ester; 4 - (1 - hydroxy - 4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert-butyl ester; (Z) -4 - (4 - O Generation -4 - Pyridin-4 - butyric -2 - enyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (4 - oxo-4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert- Ding Ester; 4 - (4 - hydroxy - 4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [4 - (2 - cyano-4 - yl) -2 - hydroxybutyrate yl] Piperidine-1 - carboxylic acid tert-butyl ester; 4 - [4 - (2 - cyano-4 - yl) -4 - hydroxy-butyl]-piperidine-1 - carboxylic acid tert-butyl ester; 4 - [4 - (2 - Cyanide Yl-4 - yl) -1 - hydroxy-butyl]-piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - oxo-4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert- Butyl; 4 - (3 - oxo-4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (4 - pyridin-4 - yl - butyryl) piperidine-1 - armor Acid tert-butyl ester; 4 - [4 - (2 - cyano-4 - yl) -2 - oxo-butyl]-piperidine-1 - carboxylic acid tert-butyl ester; 4 - [4 - (2 - cyanopyridine -4 - Yl) butanoyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [4 - (2 - cyano-4 - yl) butanoyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - Methyl-4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (1 - methyl-4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid Tert-butyl ester; 4 - [4 - (2 - cyano-4 - yl) -4 - methyl butyl amino] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [4 - (2 - cyano - pyridine -4 - Yl) -2 - methylamino - butyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (1 - dimethylamino-4 - pyridin-4 - butyl) piperidine-1 - carboxylic acid tert- Butyl; 4 - [4 - (2 - cyano-4 - yl) -4 - dimethylamino-butyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [4 - (2 - cyano- pyridine -4 - Yl) -2 - dimethylamino-butyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (2 - carbamoyl-4 - yl) ethyl] Piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (2 - ethynyl-pyridin-4 - yl) ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [(E) -4 - (2 - methyl-4 - yl) but-3 - enyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [(Z) -4 - (2 - methyl yl-4 - yl) butyl -3 - Enyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [4 - (2 - methyl-4 - yl) butyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - hydroxy -4 - [4 - (2 - methyl-4 - yl) butyl] piperidine-1 - carboxylic acid tert-butyl ester. ...

The case description of GPR119 agonist in international application case PCT/GB2005/050265 number (open) with WO2006/067532, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/GB2006/050265 number is formula (IX) chemical compound:

Or its N-oxide,

Wherein:

E ¹And E ²In one be that N and another are N or C-G ²

Dotted line forms optional double bond with solid line;

When dotted line forms two key with solid line, E ³Be CR ⁸Or N, and when it is singly-bound, E ³Be CHR ⁸, O or NR ²

T is O, S, NR ², (CH ₂) ₂Or E ⁴=E ⁵, E wherein ⁴And E ⁵Be CH or N independently;

B be key ,-CH ₂=CH ₂-or (CH ₂) _j

J is 1,2 or 3;

Q is key, C (O) S or 5 yuan or 6 yuan of hetero-aromatic rings;

A is (CH ₂) _n, one of them CH ₂Group can be through O, S, C (O), CH (OH), CH (Hal), CH (NR ²R ³), S (O), S (O) ₂Or NR ³Displacement; Two CH ₂Group can be through CH=CH, C (O) O, C (O) S, SC (O), C (O) NR ²Or OC (O) displacement; Or three CH ₂Group can be through C (O) CH ₂S, C (O) CH ₂C (OH) or C (O) CH ₂C (O) displacement;

N is 0,1,2,3,4,5 or 6;

G ¹And G ²Be hydrogen, halogen, CF independently ₃, C _1-4Alkoxyl, NR ⁴R ⁴⁴, SO ₂C _1-4Alkyl, SOC _1-4Alkyl, SC _1-4Alkyl or cyano group; Or according to circumstances through hydroxyl, NR ⁴R ⁴⁴, oxo base or C _1-4The C that alkoxyl replaces _1-4Alkyl, C _2-4Thiazolinyl or C _2-4Alkynyl;

D represents CHR ⁹Or NR ¹

R ¹Be C (O) OR ⁵, C (O) R ⁵, S (O) ₂R ⁵, C (O) NR ⁵R ¹⁰, C (O) NR ⁵R ⁵⁵, C _1-4Alkylidene-C (O) OR ⁵, C (O) C (O) OR ⁵, S (O) ₂R ⁵, C (O) R ⁵Or P (O) (O-Ph) ₂Or heterocyclic radical or heteroaryl, wherein any can replace through one or two group according to circumstances, and described group is selected from C _1-4Alkyl, C _1-4Alkoxyl, C _1-4Alkyl-OH, halogen, C _1-4Fluoroalkyl, heterocyclic radical, C (O) OC _1-4Alkyl;

R ²And R ³Be hydrogen or C independently _1-4Alkyl;

R ⁴And R ⁴⁴Be hydrogen, C independently _1-4Alkyl, C _3-7Cycloalkyl or aryl, it can replace through 1 or 2 substituent group according to circumstances, and described substituent group is selected from halogen, C _1-4Alkyl, CF ₃, C _1-4Alkoxyl, cyano group and S (O) ₂Me; Or R ⁴And R ⁴⁴Connect together and to form 5 yuan or 6 yuan of heterocycles;

R ⁵And R ⁵⁵Be C independently _1-8Alkyl, C _2-8Thiazolinyl or C _2-8Alkynyl, wherein any can be according to circumstances through one or more halogen atoms, NR ⁶R ⁶⁶, OR ⁶, C (O) OR ⁶, OC (O) R ⁶Or the cyano group replacement, and can contain through O or the metathetical CH of S ₂Group; Or C _3-7Cycloalkyl, aryl, heterocyclic radical, heteroaryl, C _1-4Alkylidene C _3-7Cycloalkyl, C _1-4Alkylidene aryl, C _1-4Alkylene heterocyclic base or C _1-4The alkylidene heteroaryl, wherein any can replace through one or more substituent groups, and described substituent group is selected from halogen, C _1-4Alkyl, C _1-4Fluoroalkyl, OR ⁷, CN, NR ⁷R ⁷⁷, SO ₂Me, NO ₂Or C (O) OR ⁷

R ⁶, R ⁶⁶, R ⁷And R ⁷⁷Be hydrogen or C independently of one another _1-4Alkyl; Or R ⁶And R ⁶⁶Or R ⁷And R ⁷⁷Connect together and to form 5 yuan or 6 yuan of heterocycles;

R ⁸Be hydrogen, hydroxyl, C _1-4Alkoxyl or benzyloxy;

R ⁹Be C _3-6Cycloalkyl;

R ¹⁰Be hydrogen or C _1-4Alkyl;

R ¹¹Be hydrogen or hydroxyl;

X is 0,1,2 or 3; And

Y is 1,2,3,4 or 5;

Condition is that x+y is 2,3,4 or 5.

International Application No. PCT/GB2005/050265 disclosed in the No. Specific examples of GPR119 agonists include the Column according to formula (IX) of the compound (referred to herein as Group I1): 4 - (furo [3,2-c] pyridin-2 - thio-carbonyl) piperazine -1 - carboxylic acid tert-butyl ester; 4 - ([1,6] naphthyridin-2 - thio-carbonyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ([1,7] naphthyridine-3 - carbonyl sulfide Yl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - (6 - chloro-1H-pyrrolo [3,2-c] pyridin-2 - thio-carbonyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - (1H-pyrrolo [2,3-c] pyridin-2 - thio-carbonyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - chloro-1H-pyrrolo [2,3-c ] pyridine -2 - Thio-carbonyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ([1,6] naphthyridin-2 - methyl-thio-carbonyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - (1H-pyrrolo [2,3-c] pyridin-2 - methyl-thio-carbonyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - (furo [3,2-c] pyridin-2 - Methyl thio carbonyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - (6 - chloro-1H-pyrrolo [3,2-c] pyridin-2 - methyl-thio-carbonyl) - piperidine - 1 - carboxylate tert-butyl ester; 4 - (5 - chloro-1H-pyrrolo [2,3-c] pyridin-2 - methyl-thio-carbonyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - ([1,7] naphthyridin-3 - methyl-thio-carbonyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (furo [3,2-c] pyridin-2 - yl methoxy) Ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (furo [3,2-c] pyridin-2 - ylmethoxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (furan And [3,2-c] pyridin-2 - yl methoxy-methyl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [3 - (furo [3,2-c] pyridin-2 - yl methoxy) Propyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [4 - (furo [3,2-c] pyridin-2 - ylmethoxy) butyl] - piperidine-1 - carboxylic acid tert-butyl Ester; 4 - (2 - furo [3,2-c] pyridin-2 - yl-ethyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - furo [3,2-c] pyridin - 2 - group Propyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - furo [2,3-c] pyridin-2 - yl-ethyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - evil Pyrazolo [4,5-c] pyridin-2 --2 - oxo - ethyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - chloro-2 - oxazolidinone [4,5 - c] pyridine-2 - Yl-ethyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (2 - oxazolo [4,5-c] pyridin-2 - yl - ethyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (4 - hydroxymethyl-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - ylmethoxy] - piperidin- - carboxylic acid tert-butyl Ester; 4 - [5 - (4 - methoxy-methyl-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - ylmethoxy] piperazine -1 - carboxylic acid tert- Butyl; 4 - [5 - (4 - dimethylaminomethyl-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - ylmethoxy ] piperidine-1 - Carboxylic acid tert-butyl ester; 4 - [5 - (4 - pyrrolidin-1 - yl methyl furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - ylmethoxy Yl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (4 - formyl-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol - ³ - methoxy- Yl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - {[(5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl ) amino] methyl Yl} - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) amino] piperidine - 1 - carboxylate tert-butyl ester; 4 - [(3 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-5 - yl methyl) amino] piperidine - 1 - carboxylate Tert-butyl ester; 4 - [ethyl-(5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) amino] - piperidin - 1 - tert- Butyl; 4 - [(5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl) propyl amino] - piperidin- - carboxylic acid tert-butyl Ester; 4 - [(5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl) methyl amino] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [(3 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-5 - yl) methyl amino] - piperidine-1 - carboxylic acid tert- butyl; 4 - [ethyl-(3 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-5 - yl methyl) amino] - piperidine-1 - carboxylic acid tert- butyl; 4 - (5 - thieno [2,3-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - thieno [3,2-c] Pyridin-2 - yl - [1,2,4] oxadiazol-3 - ylmethoxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - furo [3,2-c] pyridin - 2 - group - [1,2,4] oxadiazol-3 - yl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - furo [3,2-c] pyridin-2 - yl - [1,2 , 4] oxadiazol-3 - yl Methoxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - thieno [2,3-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - ylmethoxy yl) piperidine - 1 - carboxylate tert-butyl ester; 4 - (5 - thieno [2,3-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - thieno [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - ( 5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - thieno [3, 2-c] pyridin-2 - Yl - [1,2,4] oxadiazol-3 - yl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - [1,7] naphthyridin-3 - yl - [1,2, 4] oxadiazol-3 - yl methoxy Yl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - [1,7] naphthyridin-3 - yl - [1,2,4] oxadiazol-3 - yl) - piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - [1,7] naphthyridin-3 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - ( 1 - methyl-1H-pyrrolo [2,3-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1-carboxylic acid tert-butyl ester; 4 - [5 - (1H-pyrrolo [2,3-c] pyridine -2 - yl) - [1,2,4] oxadiazol-3 - ylmethoxy] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (1H-pyrrolo [2,3 - c] pyridine-2 - Yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - furo [2,3-c] pyridin-2 - yl - [1,2,4] oxadiazole Zol-3 - ylmethoxy) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (5 - furo [2,3-c] pyridin-2 - yl - [1,2,4] oxadiazol - ³ -) piperidine - 1 - carboxylate tert-butyl ester; 4 - [5 - (1H-pyrrolo [2,3-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl] - piperidine - 1 - carboxylate tert-butyl Ester; 4 - [5 - (7,8 - dihydro - isoquinolin-6 - yl) - [1,2,4] oxadiazol-3 - ylmethoxy] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (4 - Chloro-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - ( 4 - chloro-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - ylmethoxy] piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - furo [ 3,2-c] pyridin- -2 - Yl - [1,2,4] oxadiazol-5 - ylmethyl) piperidine-1 - carboxylic acid tert-butyl ester; 4 - (3 - furo [3,2-c] pyridin-2 - Base - [1,2,4] evil Oxadiazol-5 - ylmethoxy) piperidine-1 - carboxylic acid tert-butyl ester; (3S) -3 - (3 - furo [3,2-c] pyridin-2 - yl - [1,2,4 ] oxadiazol-5 - Ylmethoxy) pyrrolidine-1 - carboxylic acid tert-butyl ester; (3R) -3 - (3 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol - 5 - yl methyl Yloxy)-pyrrolidine-1 - carboxylic acid tert-butyl ester; 3 - (3 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-5 - ylmethoxy ) azetidinylethyl -1 - carboxylic acid tert-butyl ester; 3 - [2 - (3 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-5 - yl) - ethoxy yl] azetidin-1 - Carboxylic acid tert-butyl ester; 4 - (5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid ester ; 4 - (5 - Furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid isopropyl ester; 4 - (5 - furo [ 3,2-c] Pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid ethyl ester; 4 - (5 - furo [3,2-c] pyridin-2 - Base - [1,2,4] Oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid isobutyl ester; 4 - (5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazole -3 - group A Yl) piperidine-1 - carboxylic acid methyl cyclopropyl; 4 - (5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl ) piperidine-1 - Acid 2 - methoxycarbonyl-2 - methyl-propyl; 4 - (5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl ) piperidine - 1 - carboxylate (S) - sec-butyl; 4 - (5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperazine -1 - carboxylic acid ring Butyl; 4 - (5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid 1 - methoxy- carbonyl-1 - methyl Yl ester; 4 - (5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid 1 - A base - Ring Ding Ester; 4 - (5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid (R) - tetrahydrofuran -2 - yl Ester; 4 - (5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - acid 2 - ethoxyethyl Base - ethyl; 4 - (5 - furo [3,2-c] pyridin-2 - yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid 1 - methyl - cyclopropyl ester; 2 - [3 - (1 - Pyrimidin-2 - yl-piperidin-4 - yl methyl) - [1,2,4] oxadiazol-5 - yl] furo [3,2-c] pyridine; 4 - (5 - furo [3 ,2-c] pyridine -2 - Yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - carboxylic acid 1 - carboxy-1 - methyl ester; 4 - (5 - [3,2 -c] pyridin-2 - Yl - [1,2,4] oxadiazol-3 - yl methyl) piperidine-1 - acid 2 - carboxy-2 - methyl-propyl; 4 - [5 - (5 - oxy furo [3 ,2-c] pyridine -2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (5 - oxy furo [3,2 -c] pyridin-2 - Yl) ethyl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazole zol-3 - group A Yl] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [2 - (4 - cyano-furo [3,2-c] pyridin-2 - ylmethoxy) - ethyl] piperidine-1 - carboxylic acid uncle Butyl; 4 - [2 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) ethyl] - piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (7 - Furonitrile And [2,3-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - ylmethoxy] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (4 - Furonitrile and [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - ylmethoxy] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (4 - Thiophenecarbonitrile and [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - ylmethoxy] piperidine-1 - carboxylic acid tert-butyl ester; 4 - [5 - (4 - Furonitrile and [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid ester; 4 - [5 - (4 - cyano- furo [3,2-c] pyridine -2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid isopropyl ester; 4 - [5 - (4 - cyano-furo [3,2 -c] pyridin-2 - Yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - isobutyl; 4 - [5 - (4 - cyano-furo [3,2-c] pyridine -2 - Yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid ethyl ester; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin - ₂ -) - [1,2,4] Oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid butyl ring; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2 , 4] oxadiazole -3 - Yl methyl] piperidine-1 - carboxylic acid tetrahydropyran-4 - yl ester; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [ 1,2,4] evil Oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid (R) - sec-butyl; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [ 1,2,4] oxadiazole Zol-3 - yl methyl] piperidine-1 - carboxylic acid tetrahydrofuran-2 - yl ester; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1 2,4] Oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid (R) - tetrahydrofuran-2 - yl ester; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - Yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid (R) - tetrahydrofuran-3 - yl ester; 4 - [5 - (4 - cyano-furo [ 3,2-c] Pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid tetrahydrothiopyran-4 - yl ester; 4 - [5 - (4 - Furonitrile And [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid 1 - methoxycarbonyl-1 - methyl ester ; 4 - [5 - (4 - Cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid methoxy-methyl-carbonyl; 4 - [ 5 - (4 - Cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid methyl cyclopropyl; 4 - [ 5 - (4 - Cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - acid 3 - ethoxy - propyl; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid ( S) - sec-butyl; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid 3 - methyl - oxetane Butane -3 - yl ester; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl yl] piperidine-1 - A Acid, 2 - ethoxy - ethyl; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - Acid 2 - methoxy-1 - methyl ester; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazole -3 - yl methyl] Piperidine-1 - carboxylic acid tetrahydrofuran-3 - yl ester; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazole -3 - yl Methyl] piperidine-1 - carboxylic acid (S) - tetrahydrofuran-3 - yl ester; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2 , 4] oxadiazole Zol-3 - yl methyl] piperidine-1 - carboxylic acid tetrahydropyran-2 - yl ester; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] Oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid 1 - methyl - ring propyl; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] Oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid 1 - methyl - butyl ring; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] Oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid 1 - cyclopropyl ethyl; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] Oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid 1 - methyl - cyclopropyl methyl; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - Yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - acid 2 - methyl - cyclopropyl methyl; 4 - [5 - (4 - cyano-furo [ 3,2-c] Pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - acid 3 - methoxy-propyl; 4 - [5 - (4 - cyano-furo [3,2-c] Pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - acid 3 - acetoxy-propyl; 4 - [5 - (4 - cyano-furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid oxetan-3 - yl ester; 4 - [5 - (4 - cyano- Furo [3,2-c] pyridin-2 - yl) - [1,2,4] oxadiazol-3 - yl methyl] piperidine-1 - carboxylic acid 1 - oxo - hexahydro-1λ ...⁴-sulfo-pyrans-4-base ester; 4-[5-(4-cyano group furans is [3,2-c] pyridine-2-yl also)-[1,2,4] oxadiazole-3-ylmethyl] piperidines-1-formic acid 1,1-dioxo-six hydrogen-1 λ⁶-sulfo-pyrans-4-base ester; 4-[5-(3-benzyloxy furans is [3,2-c] pyridine-2-yl also)-[1,2,4] oxadiazole-3-ylmethyl]-piperidines-1-t-butyl formate; 4-[5-(3-hydroxyl furans is [3,2-c] pyridine-2-yl also)-[1,2,4] oxadiazole-3-ylmethyl]-piperidines-1-t-butyl formate; 4-[5-(the 4-methylfuran is [3,2-c] pyridine-2-yl also)-[1,2,4] oxadiazole-3-ylmethyl] piperidines-1-t-butyl formate; 4-[5-(the 7-iodofuran is [3,2-c] pyridine-2-yl also)-[1,2,4] oxadiazole-3-ylmethyl] piperidines-1-t-butyl formate; 4-chloro-2-[3-(1-pyrimidine-2-base piperidines-4-base oxygen ylmethyl)-[1,2,4] oxadiazole-5-yl] furans is [3,2-c] pyridine also; 2-(3-((1-(3-Methoxy Pyridine-2-yl) piperidines-4-yl) methyl)-[1,2,4]-oxadiazoles-5-yl) furans is [3,2-c] pyridine also; 6-(4-((5-(furans is [3,2-c] pyridine-2-yl also)-[1,2,4]-oxadiazoles-3-yl) methyl) piperidin-1-yl) ethyl nicotinate; 2-{3-[1-(4,6-dimethyl-pyrimidine-2-base) piperidin-4-ylmethyl]-[1,2,4] oxadiazole-5-yls }-furans [3,2-c] pyridine also; 4-(the 5-furans also [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyls)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-3 '-Ethyl formate; (the 5-furans is [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyls) piperidin-1-yl]-quinoline also for 2-[4-; (the 5-furans is [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyls) piperidin-1-yl] isoquinolin also for 1-[4-; 2-[3-(1-pyrazine-2-base-piperidin-4-ylmethyl)-[1,2,4] oxadiazole-5-yl]-furans is [3,2-c] pyridine also; 2-{3-[1-(4-methoxyl group-pyrimidine-2-base)-piperidin-4-ylmethyl]-[1,2,4] oxadiazole-5-yls }-furans [3,2-c] pyridine also; [4-(the 5-furans is [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyl also)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-5 '-yl]-methyl alcohol; 2-{3-[1-(5-ethyl-pyrimidine-2-base)-piperidin-4-ylmethyl]-[1,2,4] oxadiazole-5-yls }-furans [3,2-c] pyridine also; 2 '-chloro-4-(the 5-furans also [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyl-3,4,5,6-tetrahydrochysene-2H-[1,4 '] bipyridyl; 4 '-chloro-4-(the 5-furans also [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyls)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl; (the 5-furans is [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyls) piperidin-1-yl]-quinoxaline also for 2-[4-; 4-(the 5-furans also [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyls)-6 '-methyl-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl; 2-{3-[1-(6-methyl-pyridazine-3-yl) piperidin-4-ylmethyl]-[1,2,4] oxadiazole-5-yls } furans [3,2-c] pyridine also; [4-(the 5-furans is [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyl also)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl-4 '-yl]-methyl alcohol; 4-(the 5-furans also [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyls)-5 '-methyl-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl; 4-(the 5-furans also [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyls)-4 '-methyl-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl; 2-{3-[1-(5-propyl group-pyrimidine-2-yl)-piperidin-4-ylmethyl]-[1,2,4] oxadiazole-5-yls }-furans [3,2-c] pyridine also; 2-{3-[1-(1H-benzimidazolyl-2 radicals-yl)-piperidin-4-ylmethyl]-[1,2,4] oxadiazole-5-yl } furans [3,2-c] pyridine also; 4-(the 5-furans also [3,2-c] pyridine-2-base-[1,2,4] oxadiazole-3-ylmethyls)-3,4,5,6-tetrahydrochysene-2H-[1,2 '] bipyridyl; 2-{3-[1-(furans is [3,2-c] pyridine-4-yl also) piperidin-4-ylmethyl]-[1,2,4] oxadiazole-5-yls }-furans [3,2-c] pyridine also; 2-{3-[1-(2-chloro-pyrimidine-4-yl) piperidines-4-ylmethyl]-[1,2,4] oxadiazole-5-yls } furans [3,2-c] pyridine also; 2-{3-[1-(4-morpholine-4-base-pyrimidine-2-base)-piperidines-4-ylmethyl]-[1,2,4] oxadiazole-5-yls }-furans [3,2-c] pyridine also; 2-{3-[1-(4-trifluoromethyl-phenyl)-piperidin-4-ylmethyl]-[1,2,4] oxadiazole-5-yls } furans [3,2-c] pyridine also.

The case description of GPR119 agonist in international application case PCT/GB2005/050266 number (open) with WO2006/070208, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/GB2005/050266 number is formula (X) chemical compound:

R ¹-A-V-B-R ²

(X)

Wherein:

V is phenyl or 6 yuan of hetero-aromatic rings that contain maximum 3 N atoms;

A is-CH=CH-or (CH ₂) _n

B is-CH=CH-or (CH ₂) _n, wherein said CH ₂One in the group can be through O, NR ⁵, S (O) _m, C (O) or C (O) NR ¹²Displacement;

N is 0,1,2 or 3 independently;

M is 0,1 or 2 independently;

R ⁷Be hydrogen, C _1-4Alkyl, OR ⁶, N (R ⁶) ₂, aryl or heteroaryl;

R ⁸Be C _1-4Alkyl, C _1-4Fluoroalkyl, aryl or heteroaryl;

R ⁹Be hydrogen, C _1-2Alkyl or C _1-2Fluoroalkyl;

R ¹⁰Be hydrogen or C _1-4Alkyl;

R ¹¹It is phenyl; And

R ¹²Be hydrogen, C _1-4Alkyl or C _3-7Cycloalkyl.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/GB2005/050266 number comprises following chemical compound according to formula (X) (being referred to herein as the J1 group): 4-{[methyl-(2-pyridin-4-yl pyrimidine-4-yl)-amino] methyl } piperidines-1-t-butyl formate; 4-{[methyl-(2-pyridin-4-yl pyrimidine-4-ylmethyl) amino] methyl } piperidines-1-t-butyl formate; 4-[([2,4 '] bipyridyl-6-ylmethyl methylamino) methyl] piperidines-1-t-butyl formate.

The case description of GPR119 agonist in international application case PCT/JP02/09350 number (open) with WO 03/026661, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/JP02/09350 number is formula (XI) chemical compound:

Wherein:

-R ¹¹Be by formula-A ¹¹-D ¹¹The group of expression; A wherein ¹¹Be singly-bound, low-carbon (LC) alkylidene or low-carbon (LC) alkenylene; And D wherein ¹¹Be aryl, cycloalkyl, heteroaromatic or non-aromatic heterocycle, it can be substituted separately;

R ¹²Be-H or low-carbon alkyl, it can replace through one or more groups, described group be selected from by aryl, halogen ,-the O-low-carbon alkyl and-group that OH forms;

R ¹³Be-H, methyl or fluorine;

R ¹⁴Be-H or the low-carbon alkyl that can replace through one or more halogens; And

-R ¹⁵Be by formula-A ¹⁵-D ¹⁵The group of expression; A wherein ¹⁵Be singly-bound, low-carbon (LC) alkylidene or low-carbon (LC) alkenylene, it can be substituted separately; And D wherein ¹⁵Be-H;-O-low-carbon alkyl; Amino, it can replace through one or two group that is selected from the group that is made up of low-carbon alkyl and aryl; Or aryl, cycloalkyl, heteroaromatic or non-aromatic heterocycle, it can be substituted separately.

The case description of GPR119 agonist in international application case PCT/JP02/09350 number (open) with WO 03/026661, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/JP02/09350 number is formula (XII) chemical compound:

Wherein:

R ²¹Be aryl or heteroaromatic, it can be substituted separately;

R ²²Be methyl or ethyl;

R ²³Be-H or fluorine;

R ²⁴Be-H; And

R ²⁵Be low-carbon alkyl or cycloalkyl, it can be substituted separately.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/JP02/09350 number is following chemical compound according to formula (XII) (being referred to herein as the L1 group): 3-(2-{[2-(4-bromophenyl)-6-methylpyrimidine-4-yl] amino } ethyl) pyrrolidine 1-oxide; 2-{[2-(3-chloro-4-fluorophenyl)-6-ethyl-pyrimidine-4-yl] amino } ethanol; 3-(2-{[6-methyl-2-(3,4, the 5-trifluorophenyl) pyrimidine-4-yl] amino } ethyl) pyridine 1-oxide; 3-(2-{[2-(4-bromophenyl)-5-fluoro-6-methylpyrimidine-4-yl] amino } ethyl) pyridine 1-oxide; 3-(2-{[2-(2,1,3-Ben Bing oxadiazole-5-yl)-6-methylpyrimidine-4-yl] amino } ethyl) pyridine 1-oxide; 3-(2-{[6-ethyl-2-(3,4, the 5-trifluorophenyl) pyrimidine-4-yl] amino } ethyl) pyridine 1-oxide; 2-{[6-ethyl-2-(3,4, the 5-trifluorophenyl) pyrimidine-4-yl] amino } ethanol; 3-(2-{[2-(2, the 5-difluorophenyl)-6-methylpyrimidine-4-yl] amino } ethyl) pyridine 1-oxide; 3-(2-{[2-(2,1,3-Ben Bing oxadiazole-5-yl)-6-ethyl-pyrimidine-4-yl] amino } ethyl) pyridine 1-oxide; 3-(2-{[2-(4-chloro-2-fluorophenyl)-6-methylpyrimidine-4-yl] amino } ethyl) pyridine 1-oxide; 3-(2-{[2-(4-chloro-3-fluorophenyl)-6-methylpyrimidine-4-yl] amino } ethyl) pyridine 1-oxide; 3-(2-{[2-(5-bromo-2-fluorophenyl)-6-methylpyrimidine-4-yl] amino } ethyl) pyridine 1-oxide; 3-(2-{[6-ethyl-2-(2,3, the 5-trifluorophenyl) pyrimidine-4-yl] amino } ethyl) pyridine 1-oxide; 3-(2-{[6-methyl-2-(2,3, the 5-trifluorophenyl) pyrimidine-4-yl] amino } ethyl) pyridine 1-oxide.

The case description of GPR119 agonist in international application case PCT/JP2005/018412 number (open) with WO2006/040966, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/JP2005/018412 number is formula (XIII) chemical compound:

Wherein:

A is selected from by radicals X ¹And radicals X ²The ring of the group that forms, wherein the carbon atom that comprised of this ring can replace through one or more groups, described group be selected from by low-carbon alkyl ,-O-low-carbon alkyl, halogen, carboxyl ,-CO ₂The group that-low-carbon alkyl and carbamyl are formed;

Radicals X ¹Comprise

With

Radicals X ²Comprise

With

-R ¹It is the phenyl that replaces through at least one halogen; Wherein this phenyl can have other substituent group; And wherein work as A and be selected from radicals X ²Ring the time ,-R ¹The phenyl that expression replaces through at least three halogens;

-R ²It is group by formula (XIIIA) expression

Or the cyclic amino that is substituted according to circumstances; Wherein-R ²¹With-R ²²Identical or different and expression-H, low-carbon alkyl, low-carbon (LC) thiazolinyl, low-carbon (LC) alkynyl, cycloalkyl, phenyl, heteroaromatic, non-aromatic heterocycle or-the O-low-carbon alkyl, wherein each in these groups is substituted according to circumstances; And if wherein A is selected from radicals X ¹Ring, so-R ²The cyclic amino that expression is substituted according to circumstances.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/JP2005/018412 number is following chemical compound according to formula (XIII) (being referred to herein as the M1 group): 4-azepan-1-base-2-(4-chloro-2, the 5-difluorophenyl) thieno [3,2-d] pyrimidine; 2-(4-chloro-5-fluoro-2-piperidines-1-base phenyl)-7-methyl-4-piperidines-1-base thieno [3,2-d] pyrimidine; [2-(4-azepan-1-base thieno [3,2-d] pyrimidine-2-base)-5-chloro-4-fluorophenyl] dimethylamine; 2-{5-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl]-4,5,6,7-tetrahydrochysene-2H-pyrazolo [4,3-c] pyridine-2-yl } ethanol; 2-{5-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl]-4,5,6,7-tetrahydrochysene-1H-pyrazolo [4,3-c] pyridine-1-yl } ethanol; 1-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] and piperidines-3-yl } acetic acid; 1-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] and piperidines-4-fork } acetic acid; 2-(4-chloro-2,5-difluorophenyl)-4-piperazine-1-base thieno [3,2-d] pyrimidine; 1-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] piperidin-4-one-; 2-{4-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] piperazine-1-yl }-2-oxo ethanol; 4-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] and piperazine-1-yl } (oxo) ethyl acetate; 4-(4-acetyl group-3-methyl piperazine-1-yl)-2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine; 2-{1-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] piperidin-4-yl } acetamide; 1-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] azepan-4-alcohol; 1-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] azepan-4-formonitrile HCN; (S)-and 3-{4-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] piperazine-1-yl } the third-1, the 2-glycol; 1-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] azepan-4-ketoxime; 1-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] azepan-4-formic acid esters; (1-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] and piperidin-4-yl } the oxygen base) ethyl acetate; (4RS, 5SR)-1-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] azepan-4, the 5-glycol; 4-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] and piperazine-2-yl } methanol; 7-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] imidazolidine also [1,5-a] piperazine-1,3 (2H, 5H)-diketone; 2-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] nafoxidine also [1,2-a] piperazine-6,8 (2H, 7H)-diketone; 4-azepan-1-base-2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-6-formic acid esters; 1-[2-(4-chloro-2,5-difluorophenyl) thieno [3,2-d] pyrimidine-4-yl] and piperidin-4-yl } acetonitrile; 2-(4-chloro-2,5-difluorophenyl)-4-[4-(1H-tetrazolium-5-ylmethyl) piperidines-1-yl] thieno [3,2-d] pyrimidine; 4-azepan-1-base-2-(4-chloro-5-fluoro-2-methoxyphenyl) thieno [3,2-d] pyrimidine.

The case description of GPR119 agonist in international application case PCT/JP2005/019000 number (open) with WO2006/043490, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the GPR119 agonist in international application case PCT/JP2005/019000 number is formula (XIV) chemical compound:

Wherein:

A is selected from by radicals X ¹, radicals X ², radicals X ³And radicals X ⁴The ring of the group that forms, wherein the carbon atom that comprised of this ring can replace through one or more groups, described group be selected from by low-carbon alkyl ,-O-low-carbon alkyl, halogen, carboxyl ,-CO ₂The group that-low-carbon alkyl and carbamyl are formed; And wherein this sulphur atom of being comprised of ring can be through oxidation;

Radicals X ¹Be the group that comprises following groups:

With

Radicals X ²Be the group that comprises following groups:

With

Radicals X ³Be the group that comprises following groups:

With

Radicals X ⁴Be the group that comprises following groups:

With

-R ¹Be the group that is selected from following (1) to (3):

(1) phenyl that replaces through at least one halogen; Wherein this phenyl can have other substituent group;

(2) cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl or suberyl, it can be substituted separately;

(3) pyridine radicals, pyridazinyl, pyrimidine radicals, pyrazinyl, pyrrole radicals, thienyl, thiazolyl, oxazolyl, imidazole radicals, isothiazolyl, isoxazolyl, pyrazolyl or the furyl that replaces through at least one halogen; Wherein these rings can replace through one or more identical or different halogens; And wherein these rings are by these carbon atoms of being comprised of ring on 2 of the pyrimidine ring of bond in the formula (XIV);

Wherein work as A and be selected from radicals X ⁴Ring the time ,-R ¹The phenyl that expression replaces through at least three halogens;

-R ²It is group by formula (XIVA) expression

Or the cyclic amino that is substituted according to circumstances;

Wherein-R ²¹With-R ²²Identical or different and expression-H, low-carbon alkyl, low-carbon (LC) thiazolinyl, low-carbon (LC) alkynyl, cycloalkyl, phenyl, heteroaromatic, non-aromatic heterocycle or-the O-low-carbon alkyl, wherein each in these groups can be substituted;

Wherein work as A and be selected from radicals X ²Or radicals X ³Ring the time ,-R ²The cyclic amino that expression is substituted according to circumstances.

The particular instance of the GPR119 agonist that is disclosed in international application case PCT/JP2005/019000 number is following chemical compound according to formula (XIV) (being referred to herein as the N1 group): (R)-and 2-(4-chloro-2, the 5-difluorophenyl)-4-(3-methyl piperidine-1-yl)-5,7-dihydro-thiophene also [3,4-d] pyrimidine-6, the 6-dioxide; 4-{1-[2-(4-chloro-2,5-difluorophenyl)-6,7-dihydro-5H-cyclopenta [d] pyrimidine-4-yl] piperidin-4-yl } butanoic acid; The 7-dihydro-thiophene is [3,4-d] pyrimidine-4-yl also for 1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxo-5] and piperidines-4-fork } acetic acid; 2-(4-chloro-2,5-difluorophenyl)-4-piperazine-1-base-5, the 7-dihydro-thiophene is [3,4-d] pyrimidine also; 2-{4-[2-(4-chloro-2,5-difluorophenyl)-5, the 7-dihydro-thiophene is [3,4-d] pyrimidine-4-yl also] piperazine-1-yl }-2-oxo ethanol; 2-(4-chloro-2,5-difluorophenyl)-4-[4-(methyl sulphonyl) piperazine-1-yl]-5, the 7-dihydro-thiophene is [3,4-d] pyrimidine also; [1-(the 7-dihydro-thiophene is [3,4-d] pyrimidine-4-yl also for 2-cyclopenta-6,6-dioxo-5) piperidin-4-yl] acetamide; 1-{2-[2,5-two fluoro-4-(methyl mercapto) phenyl]-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also }-1,4-Diazesuberane-5-ketone; 4-[6,6-dioxy-4-(5-oxo-1,4-Diazesuberane-1-yl)-5, the 7-dihydro-thiophene is [3,4-d] pyrimidine-2-base also]-2, the 5-difluorobenzonitrile; 3-{1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also] piperidin-4-yl } third-1-alcohol; 2-(1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also] and piperidin-4-yl } amino) ethanol; 2-{8-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also]-2,8-diaza spiro [4.5] last of the ten Heavenly stems-2-yl } ethanol; (2Z)-3-{1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also] piperidin-4-yl } third-2-alkene-1-alcohol; (4R, 5S)-1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also] azepan-4, the 5-glycol; N-(2-amino-ethyl)-N-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also]-Beta-alanine; 1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also] and piperidin-4-yl } acetonitrile; 1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also] piperidin-4-yl (2-hydroxyethyl) methyl carbamate; 1-{1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also] piperidin-4-yl } pyrrolidin-2-one; 3-{1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also] piperidin-4-yl }-1,3-oxazolidine-2-ketone; 4-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also]-N-ethyl piperazidine-1-Methanamide; 2-(4-chloro-2,5-difluorophenyl)-N-hexamethylene-3-alkene-1-base-5, the 7-dihydro-thiophene is [3,4-d] pyrimidine-4-amine 6 also, the 6-dioxide; Acetic acid 3-{1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxy-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-yl also]-4-hydroxy piperidine-4-yl } propyl ester.

The case description of GPR119 agonist in international application case PCT/GB2006/050176 number (open) with WO2007/003960, being incorporated herein by reference in full of the disclosure of described file.

The case description of GPR119 agonist in international application case PCT/GB2006/050177 number (open) with WO2007/003961, being incorporated herein by reference in full of the disclosure of described file.

The case description of GPR119 agonist in international application case PCT/GB2006/050178 number (open) with WO2007/003962, being incorporated herein by reference in full of the disclosure of described file.

The case description of GPR119 agonist in international application case PCT/GB2006/050182 number (open) with WO2007/003964, being incorporated herein by reference in full of the disclosure of described file.

In one aspect of the invention, the GPR119 agonist is formula (I) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (II) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (III) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (IV) chemical compound.

In one aspect of the invention, the GPR119 agonist is the formula V chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (VI) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (VI) chemical compound, condition is that described chemical compound is different from 4-(5-piperidin-4-yl-[1,2,4] oxadiazole-3-yl) pyridine, 4-(3-pyridin-4-yl-[1,2,4] oxadiazole-5-yl) piperidines-1-butyl formate, 4-[5-(4-butyl cyclohexyl)-[1,2,4] oxadiazole-3-yl] pyridine, 3-[5-(4-butyl cyclohexyl)-[1,2,4] oxadiazole-3-yl] pyridine or 3-[5-(4-propyl group cyclohexyl)-[1,2,4] oxadiazole-3-yl] pyridine.

In one aspect of the invention, the GPR119 agonist is formula (VII) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (VIII) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (IX) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (X) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (XI) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (XII) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (XII) chemical compound, and condition is as R in formula (XII) ²²Be methyl and R ²³Be-during H, the R in the formula (XII) ²⁵Be not: the low-carbon alkyl that is unsubstituted; Ethyl or propyl group, its respectively hang oneself dimethylamino or diisopropylaminoethyl replacement; Through the methyl that carbamyl replaces, described carbamyl replaces through two identical or different groups, and described group is selected from the group that is made up of low-carbon alkyl and phenyl; Or the methyl that replaces through phenyl, described phenyl can be substituted.

In one aspect of the invention, the GPR119 agonist is formula (XII) chemical compound, and condition is that described chemical compound is different from 6-methyl-N-(2-morpholine-4-base ethyl)-2-phenyl pyrimidine-4-amine, 6-methyl-2-(4-methoxyphenyl)-N-(2-morpholine-4-base ethyl) pyrimidine-4-amine, 2-{[6-methyl-2-(6-picoline-2-yl) pyrimidine-4-yl] amino } ethanol, 2-{[2-(4-bromophenyl)-6-methylpyrimidine-4-yl] amino } ethanol or [2-(4-bromophenyl)-6-methylpyrimidine-4-yl] (cyclohexyl) amino.

In one aspect of the invention, the GPR119 agonist is formula (XIII) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (XIV) chemical compound.

In one aspect of the invention, the GPR119 agonist is formula (XIV) chemical compound, and condition is that described chemical compound is different from 2-(2-fluorophenyl)-N, N-dimethyl-5,7-dihydro-thiophene be [3,4-d] pyrimidine-4-amine or 2-cyclopropyl-4-piperazine-1-base-5 also, the 7-dihydro-thiophene is [3,4-d] pyrimidine also.

In one aspect of the invention, the GPR119 agonist is the chemical compound that is selected from A1 group, B1 group, B2 group, B3 group, B4 group, B5 group, C1 group, C2 group, C3 group, C4 group, C5 group, C6 group, C7 group, C8 group, C9 group, C10 group, D1 group, D2 group, D3 group, D4 group, D5 group, D6 group, D7 group, D8 group, D9 group, D10 group, D11 group, D12 group, D13 group, D14 group, E1 group, E2 group, F1 group, G1 group, G2 group, G3 group, H1 group, I1 group, J1 group, L1 group, M1 group or N1 group.

On the one hand, the GPR119 agonist is selected from the left hurdle of table D.Each indivedual GPR119 agonist of clearly containing hurdle, a table D left side all are the independent embodiment in the scope of the invention.

On the one hand, the GPR119 agonist is selected from any chemical compound group on hurdle, a table D left side.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/US2004/001267 number (open with WO04/065380) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/US2004/005555 number (open with WO04/076413) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/US2004/022327 number (open with WO05/007647) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/US2004/022417 number (open with WO05/007658) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/US2005/019318 number (open with WO2005/121121) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/GB2004/050046 number (open with WO2005/061489) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/US06/00567 number (open with WO2006/083491) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/GB2005/050264 number (open with WO2006/067531) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/GB2005/050265 number (open with WO2006/067532) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/GB2005/050266 number (open with WO2006/070208) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/JP02/09350 number (open with WO03/026661) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/JP2005/018412 number (open with WO06/040966) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/JP2005/019000 number (open with WO2006/043490) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/GB2006/050176 number (open with WO2007/003960) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/GB2006/050177 number (open with WO2007/003961) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/GB2006/050178 number (open with WO2007/003962) is identical.

On the one hand, the chemical compound that is disclosed in GPR119 agonist and the international application case PCT/GB2006/050182 number (open with WO2007/003964) is identical.

Other example of GPR119 agonist is found in international application case PCT/JP02/09350 number (open with WO03/026661), being incorporated herein by reference in full of the disclosure of described file.The GPR119 agonist that is disclosed in international application case PCT/JP02/09350 number includes, but is not limited to the chemical compound in the Table A.

Table A

The example of GPR119 agonist is found among the international application case JP 2004269468, being incorporated herein by reference in full of the disclosure of described file.The GPR119 agonist that is disclosed among the JP 2004269468 includes, but is not limited to show the chemical compound among the B.

Table B

The example of GPR119 agonist is found among the international application case JP 2004269469, being incorporated herein by reference in full of the disclosure of described file.The GPR119 agonist that is disclosed among the JP 2004269469 includes, but is not limited to show the chemical compound among the C.

Table C

On the one hand, the chemical compound that is disclosed among GPR119 agonist and the WO 03/026661 is identical.

On the one hand, the GPR119 agonist is the chemical compound that is selected from Table A.

On the one hand, the chemical compound that is disclosed among GPR119 agonist and the JP 2004269468 is identical.

On the one hand, the GPR119 agonist is the chemical compound that is selected from table B.

On the one hand, the chemical compound that is disclosed among GPR119 agonist and the JP 2004269469 is identical.

On the one hand, the GPR119 agonist is the chemical compound that is selected from table C.

In one aspect of the invention, the GPR119 agonist has less than about 10 μ M, less than about 1 μ M, less than about 100nM, less than about 75nM, less than about 50nM, less than about 25nM, less than about 20nM, less than about 15nM, less than about 10nM, less than about 5nM, less than about 4nM, less than about 3nM, less than about 2nM or less than the EC of about 1nM ₅₀In certain embodiments, the GPR119 agonist has less than about 50nM, less than about 25nM, less than about 20nM, less than about 15nM, less than about 10nM, less than about 5nM, less than about 4nM, less than about 3nM, less than about 2nM or less than the EC of about 1nM ₅₀

In one aspect of the invention, the GPR119 agonist is a selectivity GPR119 agonist, wherein said selectivity GPR119 agonist to GPR119 have be better than corticotropin releasing factor (CRF)-1 (CRF-1) receptor at least about 10 times, at least about 100 times or at least about 1000 times selectivity.In one aspect of the invention, the GPR119 agonist is a selectivity GPR119 agonist, and wherein said selectivity GPR119 agonist has GPR119 and is better than corticotropin releasing factor (CRF)-1 (CRF-1) receptor at least about 100 times selectivity.

In one aspect of the invention, the GPR119 agonist is a micromolecule.

In one aspect of the invention, GPR119 agonist tool per os activity.

The agonist that clearly to contain GPR119 agonist of the present invention be endogenous GPR119.

In one aspect of the invention, the GPR119 agonist be human GPR119 (for example, human GPR119, Deposit numbering AAP72125 and its allele) agonist.

In one aspect of the invention, can from any embodiment of the present invention, get rid of any or more than one GPR119 agonist.

The DPP-IV inhibitor

Can be used for DPP-IV inhibitor kind in the novel therapeutic combination of the present invention comprises DPP-IV is shown the chemical compound that can accept high-affinity.DPP-IV inhibitor or pharmaceutically acceptable salt can be any DPP-IV inhibitor, and are the selectivity depeptidyl peptidase inhibitors in specific embodiment, and are selective DPP-IV inhibitors in embodiment more specifically.

The case description of DPP-IV inhibitor in international application case PCT/US02/21349 number (open) with WO 03/004498, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the DPP-IV inhibitor in international application case PCT/US02/21349 number is formula (XIX) chemical compound:

Wherein:

Ar is unsubstituted or through 1-5 R ³The phenyl that replaces, wherein R ³Be independently selected from the group that forms by following each group:

(1) halogen,

(2) C _1-6Alkyl, it is straight or branched and is unsubstituted or replaces through 1-5 halogen,

(3) OC _1-6Alkyl, its be straight or branched and be unsubstituted or through 1-5 halogen replace and

(4)CN；

X is selected from the group that is made up of following each group:

(1) N and

(2)CR ²；

R ¹And R ²Be independently selected from the group that forms by following each group:

(1) hydrogen,

(2)CN，

(3) C _1-10Alkyl, it is that straight or branched and its are unsubstituted or replace through 1-5 halogen; Or phenyl, it is unsubstituted or replaces through 1-5 substituent group, and described substituent group is independently selected from halogen, CN, OH, R ⁴, OR ⁴, NHSO ₂R ⁴, SO ₂R ⁴, CO ₂H and CO ₂C _1-6Alkyl, wherein said CO ₂C _1-6Alkyl is a straight or branched,

(4) phenyl, it is unsubstituted or replaces through 1-5 substituent group, and described substituent group is independently selected from halogen, CN, OH, R ⁴, OR ⁴, NHSO ₂R ⁴, SO ₂R ⁴, CO ₂H and CO ₂C _1-6Alkyl, wherein said CO ₂C _1-6Alkyl be straight or branched and

(5) 5 yuan or 6 yuan of heterocycles, it can be saturated or unsaturated heterocycle, and it comprises 1-4 hetero atom that independently is selected from N, S and O, and described heterocycle is unsubstituted or replaces through 1-3 substituent group, and described substituent group is independently selected from oxo base, OH, halogen, C _1-6Alkyl and OC _1-6Alkyl, wherein said C _1-6Alkyl and OC _1-6Alkyl is straight or branched and replaces through 1-5 halogen according to circumstances;

R ⁴Be C _1-6Alkyl, it is that straight or branched and its are unsubstituted or replace through 1-5 group, described group is independently selected from halogen, CO ₂H and CO ₂C _1-6Alkyl, wherein said CO ₂C _1-6Alkyl is a straight or branched.

The particular instance of the DPP-IV inhibitor that is disclosed in international application case PCT/US02/21349 number comprises following chemical compound according to formula (XIX) (being referred to herein as the S1 group): 7-[(3R)-and 3-amino-4-(3, the 4-difluorophenyl) bytyry]-2-(trifluoromethyl)-5,6,7, the 8-imidazolidine is [1,2-a] pyrazine also; 7-[(3R)-3-amino-4-(2, the 5-difluorophenyl) bytyry]-2-(trifluoromethyl)-5,6,7, the 8-imidazolidine is [1,2-a] pyrazine also; 7-[(3R)-3-amino-4-(2,4, the 5-trifluorophenyl) bytyry]-2-(trifluoromethyl)-5,6,7, the 8-imidazolidine is [1,2-a] pyrazine also; 7-[3 (R)-3-amino-4-(3, the 4-difluorophenyl) bytyry]-5,6,7, the 8-imidazolidine is [1,2-a] pyrazine also; 7-[(3R)-3-amino-4-(3, the 4-difluorophenyl) bytyry]-3-ethyl-5,6,7,8-tetrahydrochysene-1,2,4-triazol [4,3-a] pyrazine; 7-[(3R)-3-amino-4-(2, the 5-difluorophenyl) bytyry]-3-(trifluoromethyl)-5,6,7,8-tetrahydrochysene-1,2,4-triazol [4,3-a] pyrazine; 7-[(3R)-3-amino-4-(2,4, the 5-trifluorophenyl) bytyry]-3-(trifluoromethyl)-5,6,7,8-tetrahydrochysene-1,2,4-triazol [4,3-a] pyrazine.

The case description of DPP-IV inhibitor in international application case PCT/EP99/09708 number (open) with WO 00/34241, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the DPP-IV inhibitor among the international application case PCT/EP99/09708 is formula (XX) chemical compound:

Wherein:

R is the adamantyl that is substituted; And

N is 0 to 3.

The particular instance of the DPP-IV inhibitor that is disclosed in international application case PCT/EP99/09708 number comprises following chemical compound according to formula (XX) (being referred to herein as the T1 group): pyrrolidine, 1-[[(3,5-dimethyl-1-adamantyl) amino]-acetyl group]-2-cyano group-, (S)-; Pyrrolidine, 1-[[(3-ethyl-1-adamantyl) amino] acetyl group]-2-cyano group-, (S)-; Pyrrolidine, 1-[[(3-methoxyl group-1-adamantyl) amino]-acetyl group]-2-cyano group-, (S)-; Pyrrolidine, 1-[[[3-[[(tert-butyl group amino) carbonyl] the oxygen base]-the 1-adamantyl] amino] acetyl group]-2-cyano group-, (S)-; Pyrrolidine, the 1-[[[3-[[[(4-methoxyphenyl) amino] carbonyl] the oxygen base]-the 1-adamantyl] amino] acetyl group]-2-cyano group-, (S)-; Pyrrolidine, the 1-[[[3-[[(phenyl amino) carbonyl] the oxygen base]-the 1-adamantyl] amino] acetyl group]-2-cyano group-, (S)-; Pyrrolidine, 1-[[(5-hydroxyl-2-adamantyl) amino]-acetyl group]-2-cyano group-, (S)-; Pyrrolidine, 1-[[(3-acetyl group Oxy-1-adamantyl) amino]-acetyl group]-2-cyano group-, (S)-; Pyrrolidine, the 1-[[[3-[[[(diisopropyl) amino] carbonyl] the oxygen base]-the 1-adamantyl] amino] acetyl group]-2-cyano group-, (S)-; Pyrrolidine, the 1-[[[3-[[[(cyclohexyl) amino] carbonyl] the oxygen base]-the 1-adamantyl] amino] acetyl group]-2-cyano group-, (S)-; Pyrrolidine, 1-[[(3-ethyoxyl-1-adamantyl) amino] acetyl group]-2-cyano group-, (S)-.

The case description of DPP-IV inhibitor in international application case PCT/US01/07151 number (open) with WO 01/68603, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the DPP-IV inhibitor in international application case PCT/US01/07151 number is formula (XXI) chemical compound:

Wherein:

X be 0 or 1 and y be 0 or 1, condition is:

When y=0, x=1, and

When y=1, x=0;

N is 0 or 1;

X is H or CN;

R ¹, R ², R ³And R ⁴Identical or different and be independently selected from assorted alkyl of hydrogen, alkyl, thiazolinyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, bicyclic alkyl, tricyclic alkyl, alkyl-cycloalkyl, hydroxy alkyl, hydroxy alkyl cycloalkyl, hydroxyl cycloalkyl, hydroxyl bicyclic alkyl, hydroxyl tricyclic alkyl, bicyclic alkyl alkyl, alkyl sulfenyl alkyl, aryl alkyl sulfenyl alkyl, cycloalkenyl group, aryl, aralkyl, heteroaryl, heteroaryl alkyl, ring or the assorted alkyl-alkyl of ring; It all passes through available carbon atom according to circumstances through 1,2,3,4 or 5 groups replace, and described group is selected from hydrogen, halogen, alkyl, poly-alkylhalide group, alkoxyl, the halogen alkoxyl, poly-halogen alkoxyl, alkoxy carbonyl group, thiazolinyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, poly-cycloalkyl, heteroaryl amino, arylamino, the assorted alkyl of ring, the assorted alkyl-alkyl of ring, hydroxyl, hydroxy alkyl, nitro, cyano group, amino, be substituted amino, alkyl amino, dialkyl amido, mercaptan, the alkyl sulfenyl, alkyl-carbonyl, acyl group, alkoxy carbonyl group, amino carbonyl, the alkynyl amino carbonyl, alkyl amino-carbonyl, the alkenyl amino carbonyl, alkyl carbonyl oxy, alkyl-carbonyl-amino, aryl-amino-carbonyl, alkyl sulfonyl-amino, alkyl amino-carbonyl amino, alkoxycarbonyl amido, alkyl sulphonyl, amino sulfinyl, amino-sulfonyl, alkyl sulphinyl, sulfoamido or sulfonyl;

And R ¹And R ³Can form together according to circumstances-(CR ⁵R ⁶) _m-, wherein m is 2 to 6, and R ⁵And R ⁶Identical or different and be independently selected from hydroxyl, alkoxyl, H, alkyl, thiazolinyl, alkynyl, cycloalkyl, halogen, amino, be substituted amino, cycloalkyl-alkyl, cycloalkenyl group, aryl, aryl alkyl, heteroaryl, heteroaryl alkyl, the assorted alkyl of ring, the assorted alkyl-alkyl of ring, alkyl-carbonyl-amino, aryl-amino-carbonyl, alkoxycarbonyl amido, aryloxy carbonyl amino, alkoxy carbonyl group, aryloxy carbonyl or alkyl amino-carbonyl amino, or R ¹And R ⁴Can form together according to circumstances-(CR ⁷R ⁸) _p-, wherein p is 2 to 6, and R ⁷And R ⁸Identical or different and be independently selected from hydroxyl, alkoxyl, cyano group, H, alkyl, thiazolinyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, cycloalkenyl group, halogen, amino, be substituted amino, aryl, aryl alkyl, heteroaryl, heteroaryl alkyl, the assorted alkyl of ring, the assorted alkyl-alkyl of ring, alkyl-carbonyl-amino, aryl-amino-carbonyl, alkoxycarbonyl amido, aryloxy carbonyl amino, alkoxy carbonyl group, aryloxy carbonyl or alkyl amino-carbonyl amino, or R according to circumstances ¹And R ³With

Form together and contain 2 to 4 altogether and be selected from N, O, S, SO or SO ₂Heteroatomic 5 yuan to 7 yuan rings;

Or R according to circumstances ¹And R ³With

Form 4 yuan to the 8 yuan assorted alkyl rings of ring together, the assorted alkyl ring of wherein said ring has with it condensed optional aromatic ring or condensed optional 3 yuan to 7 yuan cycloalkyl rings with it.

The case description of DPP-IV inhibitor in international application case PCT/US2004/042209 number (open) with WO2005/095381, being incorporated herein by reference in full of the disclosure of described file.What be disclosed as the DPP-IV inhibitor in international application case PCT/US2004/042209 number is formula (XXII) chemical compound:

Wherein:

M ₀Be-C-LX, N or CR ₄

Q ¹And Q ²Be selected from independently of one another by CO, CS, SO, SO ₂And C=NR ₉The group that forms;

R ₀Be R ₁Or-LX, condition is R ₀And M ₀In only have one to be-LX;

R ₁Be hydrogen or be selected from by halogen, perhalogeno (C _1-10) alkyl, amino, cyano group, sulfenyl, (C _1-10) alkyl, cycloalkyl, Heterocyclylalkyl, aryl alkyl, heteroaryl alkyl, aryl, heteroaryl, carbonyl (C _1-3) alkyl, thiocarbonyl (C _1-3) alkyl, sulfonyl (C _1-3) alkyl, sulfinyl (C _1-3) alkyl, imino group (C _1-3) group that alkyl, hydroxyl, alkoxyl, aryloxy group, heteroaryloxy, carbonyl, imino group, sulfonyl and sulfinyl are formed, each group is substituted or is unsubstituted;

R ₂Be hydrogen or be selected from by (C _1-10) alkyl, (C _3-12) cycloalkyl, (C _3-12) cycloalkyl (C _1-5) alkyl, assorted (C _3-12) cycloalkyl (C _1-5) alkyl, assorted (C _3-12) cycloalkyl, aryl (C _1-10) alkyl, heteroaryl (C _1-5) alkyl, (C _9-12) bicyclic aryl, assorted (C _4-12) bicyclic aryl, assorted (C _4-12) bicyclic aryl (C _1-5) alkyl, carbonyl (C _1-3) alkyl, thiocarbonyl (C _1-3) alkyl, sulfonyl (C _1-3) alkyl, sulfinyl (C _1-3) alkyl, imino group (C _1-3) group that alkyl, amino, aryl, heteroaryl, hydroxyl, alkoxyl, aryloxy group, heteroaryloxy, carbonyl, imino group, sulfonyl and sulfinyl are formed, each group is substituted or is unsubstituted;

R ₃Be selected from by perhalogeno (C _1-10) alkyl, amino, (C _1-10) alkyl, cycloalkyl, Heterocyclylalkyl, aryl alkyl, heteroaryl alkyl, aryl, heteroaryl, carbonyl (C _1-3) alkyl, thiocarbonyl (C _1-3) alkyl, sulfonyl (C _1-3) alkyl, sulfinyl (C _1-3) alkyl, imino group (C _1-3) group that alkyl, hydroxyl, alkoxyl, aryloxy group, heteroaryloxy, carbonyl, imino group, sulfonyl and sulfinyl are formed, each group is substituted or is unsubstituted; And 3 yuan, 4 yuan, 5 yuan, 6 yuan or 7 yuan of rings being substituted or being unsubstituted;

R ₄Be hydrogen or be selected from by halogen, perhalogeno (C _1-10) alkyl, amino, cyano group, sulfenyl, (C _1-10) alkyl, cycloalkyl, Heterocyclylalkyl, aryl alkyl, heteroaryl alkyl, aryl, heteroaryl, carbonyl (C _1-3) alkyl, thiocarbonyl (C _1-3) alkyl, sulfonyl (C _1-3) alkyl, sulfinyl (C _1-3) alkyl, imino group (C _1-3) group that alkyl, hydroxyl, alkoxyl, aryloxy group, heteroaryloxy, carbonyl, imino group, sulfonyl and sulfinyl are formed, each group is substituted or is unsubstituted;

R ₉Be hydrogen or be selected from the group that forms by alkyl, cycloalkyl, Heterocyclylalkyl, aryl alkyl, heteroaryl alkyl, bicyclic aryl and assorted bicyclic aryl that each group is substituted or is unsubstituted;

L provides the connection base of 1,2 or 3 atomic separation between X and the ring that L is connected, the group that the wherein said atom that connection base at interval is provided selects free carbon, oxygen, nitrogen and sulfur to form; And

X is selected from by (C _1-10) alkyl, (C _3-12) cycloalkyl, assorted (C _3-12) cycloalkyl, aryl (C _1-10) alkyl, heteroaryl (C _1-5) alkyl, (C _9-12) bicyclic aryl, assorted (C _4-12) bicyclic aryl, carbonyl (C _1-3) alkyl, thiocarbonyl (C _1-3) alkyl, sulfonyl (C _1-3) alkyl, sulfinyl (C _1-3) alkyl, imino group (C _1-3) group that alkyl, amino, aryl, heteroaryl, hydroxyl, alkoxyl, aryloxy group, heteroaryloxy, thiazolinyl, alkynyl, carbonyl, cyano group, imino group, sulfonyl and sulfinyl are formed, each group is substituted or is unsubstituted.

The particular instance of the DPP-IV inhibitor that is disclosed in international application case PCT/US2004/042209 number comprises following chemical compound according to formula (XXII) (being referred to herein as the V1 group): 2-(6-chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl)-benzonitrile; 2-(6-chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl)-benzonitrile; 2-{6-[3-amino-piperadine-1-yl]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-{6-[3-amino-piperadine-1-yl]-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl } benzonitrile; 2-{6-[3-amino-piperadine-1-yl]-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-{6-[3-amino-piperadine-1-yl]-5-chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 6-[3-amino-piperadine-1-yl]-1-(2-bromo-benzyl)-1H-pyrimidine-2, the 4-diketone; 6-[3-amino-piperadine-1-yl]-1-(2-iodo-benzyl)-1H-pyrimidine-2, the 4-diketone; 6-[3-amino-piperadine-1-yl]-1-(2-bromo-5-fluoro-benzyl)-3-methyl isophthalic acid H-pyrimidine-2, the 4-diketone; 6-[3-amino-piperadine-1-yl]-1-(2-chloro-5-fluoro-benzyl)-3-methyl isophthalic acid H-pyrimidine-2, the 4-diketone; 6-[3-amino-piperadine-1-yl]-1-(2-chloro-4-fluoro-benzyl)-3-methyl isophthalic acid H-pyrimidine-2, the 4-diketone; 6-[3-amino-piperadine-1-yl]-1-(2-bromo-benzyl)-3-methyl isophthalic acid H-pyrimidine-2, the 4-diketone; 2-{6-[azepan-3 (±)-Ji amino]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-{6-[3 (±)-amino-azepan-1-yl]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-[6-(2-amino-ethyl amino)-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl]-benzonitrile; 2-{6-[3-amino-piperadine-1-yl]-3-(3-cyano group-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-{6-[3-amino-piperadine-1-yl]-3-(2-cyano group-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-{6-[3-amino-piperadine-1-yl]-3-(4-cyano group-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl } benzonitrile; 2-[6-(3-amino-piperadine-1-yl)-3-(1H-benzimidazolyl-2 radicals-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl]-benzonitrile; 2-{6-[3-amino-piperadine-1-yl]-2,4-dioxo-3-(4-pyrazol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-{6-[3-amino-piperadine-1-yl]-2,4-dioxo-3-(3-pyrroles-1-base-benzyl)-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 6-[3-amino-piperadine-1-yl]-3-(2-cyano group-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidine-1-ylmethyl]-thiophene-3-formonitrile HCN; 3-{4-[3-amino-piperadine-1-yl]-3-(2-cyano group-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidine-1-ylmethyl }-essence of Niobe; 3-{4-[3-amino-piperadine-1-yl]-3-(2-cyano group-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidine-1-ylmethyl }-benzoic acid; 6-[3-amino-piperadine-1-yl]-1,3-pair-(2-bromo-5-fluoro-benzyl)-1H-pyrimidine-2, the 4-diketone; 2-{6-[3 (R)-amino-piperadine-1-yl]-5-chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 6-[3 (R)-amino-piperadine-1-yl]-1-(2,5-two chloro-benzyls)-3-methyl isophthalic acid H-pyrimidine-2, the 4-diketone; 6-[3 (R)-amino-piperadine-1-yl]-1-(2-chloro-3,6-two fluoro-benzyls)-3-methyl isophthalic acid H-pyrimidine-2, the 4-diketone; (R)-2-((6-(3-amino-3-methyl piperidine-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-pyrimidin-1 (2H)-yl) methyl)-4-fluorobenzonitrile; 2-[6-(3-amino-piperadine-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl]-4-fluoro-benzonitrile.

The particular instance of the DPP-IV inhibitor that is disclosed in international application case PCT/US2004/042209 number comprises following chemical compound according to formula (XXII) (being referred to herein as the V2 group): 2-{6-[3 (R)-amino-piperadine-1-yl]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl } benzonitrile; 2-{6-[3 (R)-amino-piperadine-1-yl]-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-{6-[3 (R)-amino-piperadine-1-yl]-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-{6-[3 (R)-amino-piperadine-1-yl]-5-chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 6-[3 (R)-amino-piperadine-1-yl]-1-(2-bromo-benzyl)-1H-pyrimidine-2, the 4-diketone; 6-[3 (R)-amino-piperadine-1-yl]-1-(2-iodo-benzyl)-1H-pyrimidine-2, the 4-diketone; 6-[3 (R)-amino-piperadine-1-yl]-1-(2-bromo-5-fluoro-benzyl)-3-methyl isophthalic acid H-pyrimidine-2, the 4-diketone; 6-{[3 (R)-amino-piperadine-1-yl]-1-(2-chloro-5-fluoro-benzyl)-3-methyl isophthalic acid H-pyrimidine-2, the 4-diketone; 6-[3 (R)-amino-piperadine-1-yl]-1-(2-chloro-4-fluoro-benzyl)-3-methyl isophthalic acid H-pyrimidine-2, the 4-diketone; 6-[3 (R)-amino-piperadine-1-yl]-1-(2-bromo-benzyl)-3-methyl isophthalic acid H-pyrimidine-2, the 4-diketone; 2-{6-[3 (R)-amino-piperadine-1-yl]-3-(3-cyano group-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-{6-[3 (R)-amino-piperadine-1-yl]-3-(2-cyano group-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-{6-[3 (R)-amino-piperadine-1-yl]-3-(4-cyano group-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1 ylmethyl }-benzonitrile; 2-[6-(3-amino-piperadine-1-yl)-3-(1H-benzimidazolyl-2 radicals-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl]-benzonitrile; 2-{6-[3 (R)-amino-piperadine-1-yl]-2,4-dioxo-3-(4-pyrazol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidine-1-ylmethyl }-benzonitrile; 2-{6-[3 (R)-amino-piperadine-1-yl]-2,4-dioxo-3-(3-pyrroles-1-base-benzyl)-3,4-dihydro-2H-pyrimidine-1-ylmethyl)-benzonitrile; 6-[3 (R)-amino-piperadine-1-yl]-3-(2-cyano group-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidine-1-ylmethyl]-thiophene-3-formonitrile HCN; 3-{4-[3 (R)-amino-piperadine-1-yl]-3-(2-cyano group-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidine-1-ylmethyl }-essence of Niobe; 3-{4-[3 (R)-amino-piperadine-1-yl]-3-(2-cyano group-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidine-1-ylmethyl }-benzoic acid; 6-[3 (R)-amino-piperadine-1-yl]-1,3-pair-(2-bromo-5-fluoro-benzyl)-1H-pyrimidine-2, the 4-diketone; 2-[6-(3 (R)-amino-piperadine-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-ylmethyl]-4-fluoro-benzonitrile.

The case description of DPP-IV inhibitor is in Wei Haoer people such as (Vi1lhauer), and pharmaceutical chemistry magazine (J Med Chem) (2003) 46:2774-2789 is about LAF237; Allan people such as (Ahren), clinical endocrine metabolism magazine (J C1inEndocrinol Metab) (2004) 89:2078-2084; Tie up great that people such as (Vi1lhauer), pharmaceutical chemistry magazine (J MedChem) (2002) 45:2362-2365 is about NVP-DPP728; Allan people such as (Ahren), diabetes care (DiabetesCare) (2002) 25:869-875 is about NVP-DPP728; Peter people such as (Peters), bioorganic pesticide thing chemistry wall bulletin (Bioorg Med Chem Lett) (2004) 14:1491-1493; Caldwell people such as (Caldwell), bioorganic pesticide thing chemistry wall bulletin (Bioorg Med Chem Lett) (2004) 14:1265-1268; Edmondson people such as (Edmondson), bioorganic pesticide thing chemistry wall bulletin (Bioorg Med Chem Lett) (2004) 14:5151-5155; And Abel people such as (Abe), natural product magazine (J Nat Prod) (2004) 67:999-1004; Being incorporated herein by reference in full of the disclosure of described each file.

The particular instance of DPP-IV inhibitor includes, but is not limited to dipeptidase derivant or dipeptide analogue; for example alanine-pyrrolidine (alanine-pyrrolidide), isoleucine-Thiazolidine (isoleucine-thiazolidide); and the valyl prolyl of counterfeit substrate N-; O-benzoyl azanol; as for example United States Patent (USP) the 6th; described in 303, No. 661, being incorporated herein by reference in full of the disclosure of described file.

The example of DPP-IV inhibitor is found in United States Patent (USP) the 7th, 074, No. 794, the 7th, 060, No. 722, the 7th, 053, No. 055, the 7th, 026, No. 316, the 7th, 022, No. 718, the 6th, 949, No. 515, the 6th, 897, No. 222, the 6th, 869, No. 947, the 6th, 867, No. 205, the 6th, 861, No. 440, the 6th, 849, No. 622, the 6th, 812, No. 350, the 6th, 803, No. 357, the 6th, 800, No. 650, the 6th, 727, No. 261, the 6th, 716, No. 843, the 6th, 710, No. 040, the 6th, 706, No. 742, the 6th, 645, No. 995, the 6th, 617, No. 340, the 6th, 699, No. 871, the 6th, 573, No. 287, the 6th, 432, No. 969, the 6th, 395, No. 767, the 6th, 380, No. 398, the 6th, 303, No. 661, the 6th, 242, No. 422, the 6th, 166, No. 063, the 6th, 100, No. 234, in the 6th, 040, No. 145, being incorporated herein by reference in full of the disclosure of described each file.The example of DPP-IV inhibitor is found in U.S. patent application case No. 2006142576, No. 2006135767, No. 2006135512, No. 2006111336, No. 2006074087, No. 2006069116, No. 2006052382, No. 2006046978, No. 2006040963, No. 2006039974, No. 2006024313, No. 2006014764, No. 2005059724, No. 2005059716, No. 2005043292, No. 2005038020, No. 2005032804, No. 2005004205, No. 2004259903, No. 2004259902, No. 2004259883, No. 2004254226, No. 2004242898, No. 2004229926, No. 2004180925, No. 2004176406, No. 2004138214, No. 2004116328, No. 2004110817, No. 2004106656, No. 2004097510, No. 2004087587, No. 2004082570, No. 2004077645, No. 2004072892, No. 2004063935, No. 2004034014, No. 2003232788, No. 2003225102, No. 2003216450, No. 2003216382, No. 2003199528, No. 2003195188, No. 2003162820, No. 2003149071, No. 2003134802, No. 2003130281, No. 2003130199, No. 2003125304, No. 2003119750, No. 2003119738, No. 2003105077, No. 2003100563, No. 2003087950, No. 2003078247, No. 2002198205, No. 2002183367, No. 2002103384, No. 2002049164, in No. 2002006899, being incorporated herein by reference in full of the disclosure of described each file.

The example of DPP-IV inhibitor is found in international application case WO 2006/071762, WO 2006/071752, WO2006/068978, WO 2006/068163, WO 2006/058628, WO 2006/058064, WO 2006/040625, WO 2006/039325, WO 2006/033848, WO 2006/030847, WO 2006/027204, WO2006/023750, WO 2006/020017, WO 2006/015699, WO 2006/015691, WO 2006/013104, WO 2006/012441, WO 2006/012395, WO 2006/011035, WO 2006/009886, WO2005/123685, WO 2005/121131, WO 2005/121089, WO 2005/120494, WO 2005/118555, WO 2005/116029, WO 2005/116014, WO 2005/115982, WO 2005/108382, WO2005/106011, WO 2005/100334, WO 2005/095339, WO 2005/094323, WO 2005/087235, WO 2005/082849, WO 2005/082348, WO 2005/079795, WO 2005/075426, WO2005/072530, WO 2005/063750, WO 2005/058849, WO 2005/049022, WO 2005/047297, WO 2005/044195, WO 2005/042533, WO 2005/042488, WO 2005/040095, WO2005/037828, WO 2005/037779, WO 2005/034940, WO 2005/033099, WO 2005/032590, WO 2005/030751, WO 2005/030127, WO 2005/026148, WO 2005/025554, WO2005/023762, WO 2005/020920, WO 05/19168, WO 05/12312, WO 05/12308, WO05/12249, WO 05/11581, WO 05/09956, WO 05/03135, WO 05/00848, WO 05/00846, WO 04/112701, WO 04/111051, WO 04/111041, WO 04/110436, WO 04/110375, WO04/108730, WO 04/104216, WO 04/104215, WO 04/103993, WO 04/103276, WO 04/99134, WO 04/96806, WO 04/92128, WO 04/87650, WO 04/87053, WO 04/85661, WO 04/85378, WO 04/76434, WO 04/76433, WO 04/71454, WO 04/69162, WO 04/67509, WO 04/64778, WO 04/58266, WO 04/52362, WO 04/52850, WO 04/50022, WO 04/50658, WO 04/48379, WO 04/46106, WO 04/43940, WO 04/41820, WO 04/41795, WO 04/37169, WO 04/37181, WO 04/33455, WO 04/32836, WO 04/20407, WO 04/18469, WO 04/18468, WO 04/18467, WO 04/14860, WO 04/09544, WO 04/07468, WO 04/07446, WO 04/04661, WO 04/00327, WO 03/106456, WO 03/104229, WO 03/101958, WO 03/101448, WO 03/99279, WO03/95425, WO 03/84940, WO 03/82817, WO 03/80633, WO 03/74500, WO 03/72556, WO 03/72528, WO 03/68757, WO 03/68748, WO 03/57666, WO 03/57144, WO 03/55881, WO 03/45228, WO 03/40174, WO 03/38123, WO 03/37327, WO 03/35067, WO 03/35057, WO 03/24965, WO 03/24942, WO 03/22871, WO 03/15775, WO 03/04498, WO 03/04496, WO 03/02530, WO 03/02596, WO 03/02595, WO 03/02593, WO 03/02553, WO 03/02531, WO 03/00181, WO 03/00180, WO 03/00250, WO 02/83109, WO 02/83128, WO 02/76450, WO 02/68420, WO 02/62764, WO 02/55088, WO 02/51836, WO 02/38541, WO 02/34900, WO 02/30891, WO 02/30890, WO 02/14271, WO 02/02560, WO 01/97808, WO 01/96295, WO 01/81337, WO 01/81304, WO 01/68603, WO 01/55105, WO 01/52825, WO 01/34594, WO 00/71135, WO 00/69868, WO 00/56297, WO 00/56296, WO 00/34241, WO 00/23421, WO 00/10549, WO 99/67278, WO 99/62914, WO 99/61431, WO 99/56753, WO 99/25719, WO 99/16864, WO 98/50066, WO 98/50046, WO 98/19998, WO 98/18763, WO 97/40832, WO 95/29691, WO 95/15309, WO 93/10127, WO 93/08259, WO 91/16339, EP 1671649, EP 1667524, EP 1664031, EP 1659123, EP 1658066, EP 1638970, EP 1638968, EP 1638950, EP 1635818, EP 1627870, EP 1625122, EP 1624874, EP 1517907, EP 1513808, EP 1492777, EP 1490335, EP 1489088, EP 1480961, EP 1476435, EP 1476429, EP 1469873, EP 1465891, EP 1463727, EP 1461337, EP 1450794, EP 1446116, EP 1442049, EP 1441719, EP 1426366, EP 1412357, EP 1406873, EP 1406872, EP 1406622, EP 1404675, EP 1399420, EP 1399471, EP 1399470, EP 1399469, EP 1399433, EP 1399154, EP 1385508, EP 1377288, EP 1355886, EP 1354882, EP 1338592, EP 1333025, EP 1323710, EP 1304327, EP 1301187, EP 1296974, EP 1280797, EP 1282600, EP 1261586, EP 1258476, EP 1254113, EP 1248604, EP 1245568, EP 1215207, EP 1228061, EP 1137635, EP 1123272, EP 1104293, EP 1082314, EP 1050540, EP 1043328, EP 0995440, EP 0980249, EP 0975359, EP 0731789, EP 0641347, EP 0610317, EP 0528858, CA 2466870, CA 2433090, CA 2339537, CA 2289125, CA 2289124, CA2123128, DD 296075, DE 19834591, DE 19828113, DE 19823831, DE 19616486, DE10333935, DE 10327439, DE 10256264, DE 10251927, DE 10238477, DE 10238470, DE 10238243, DE 10143840, FR 2824825, FR 2822826, JP 2005507261, JP 2005505531, JP 2005502624, JP 2005500321, JP 2005500308, JP 2005023038, JP 2004536115, JP2004535445, JP 2004535433, JP 2004534836, JP 2004534815, JP 2004532220, JP2004530729, JP 2004525929, JP 2004525179, JP 2004522786, JP 2004521149, JP2004503531, JP 2004315496, JP 2004244412, JP 2004043429, JP 2004035574, JP2004026820, JP 2004026678, JP 2004002368, JP 2004002367, JP 2003535898, JP2003535034, JP 2003531204, JP 2003531191, JP 2003531118, JP 2003524591, JP2003520849, JP 2003327532, JP 2003300977, JP 2003238566, JP 200253154/, JP2002527504, JP 2002517401, JP 2002516318, JP 2002363157, JP 2002356472, JP2002356471, JP 2002265439, JP 2001510442, JP 2000511559, JP 2000327689, JP2000191616, JP 1998182613, JP 1998081666, JP 1997509921, JP 1995501078, among the JP1993508624, being incorporated herein by reference in full of the disclosure of described each file.

In one aspect of the invention, the DPP-IV inhibitor is valine-pyrrolidine (Deacon people such as (Deacon), diabetes (Diabetes) (1998) 47:764-769; Being incorporated herein by reference in full of its disclosure).

In one aspect of the invention, the DPP-IV inhibitor is 3-(L-isoleucyl-) Thiazolidine (isoleucine-Thiazolidine).Isoleucine-Thiazolidine is found among JP 2001510442, WO 97/40832, US 6,303,661 and the DE 19616486, being incorporated herein by reference in full of the disclosure of described each file.Isoleucine-Thiazolidine is through being described as having active and DPP-IV inhibitor [Pi Desen people such as (Pederson), diabetes (Diabetes) (1998) 47:1253-1258 optionally of per os; Being incorporated herein by reference in full of its disclosure].

In one aspect of the invention, the DPP-IV inhibitor is 1-[2-[5-cyanopyridine-2-yl) amino] ethylamino] acetyl group-2-cyano group-(S)-pyrrolidine (NVP-DPP728).NVP-DPP728 is found among WO 98/19998 and the JP2000511559, being incorporated herein by reference in full of the disclosure of described each file.NVP-DPP728 is through being described as having the active and DPP-IV inhibitor [Wei Haoer people such as (Villhauer), pharmaceutical chemistry magazine (J Med Chem) (2002) 45:2362-2365] optionally of per os.

In one aspect of the invention, the DPP-IV inhibitor is 3 (R)-amino-1-[3-(trifluoromethyl)-5,6,7,8-tetrahydrochysene [1,2,4] triazol [4,3-a] pyrazine-7-yl]-4-(2,4, the 5-trifluorophenyl) fourth-1-ketone (MK-0431; Sitagliptin).MK-0431 is found among EP 1412357, WO 03/04498, US 6,699,871 and the US 2003100563, being incorporated herein by reference in full of the disclosure of described each file.MK-0431 is through being described as having the active and DPP-IV inhibitor [weber people such as (Weber), Diabetes (2004) 53 (supplementary issue 2): A151,633-P (summary), being incorporated herein by reference in full of its disclosure] optionally of per os.

In one aspect of the invention, the DPP-IV inhibitor is (1-[[3-hydroxyl-1-adamantyl) amino] acetyl group]-2-cyano group-(S)-pyrrolidine (LAF237; Vildagliptin).LAF237 is found in US 6,166, and 063, among WO 00/34241, EP1137635 and the JP 2002531547, being incorporated herein by reference in full of the disclosure of described each file.LAF237 is through being described as having the active and DPP-IV inhibitor [Wei Haoer people such as (Villhauer), pharmaceutical chemistry magazine (J Med Chem) (2003) 46:2774-2789] optionally of per os.

In one aspect of the invention, the DPP-IV inhibitor be (1S, 3S, 5S)-2-[2 (S)-amino-2-(3-hydroxyadamantane-1-yl) acetyl group]-2-azabicyclo [3.1.0] hexane-3-formonitrile HCN (BMS-477118; Sa Kelieting).

In one aspect of the invention, the DPP-IV inhibitor is [1-[2 (S)-amino-3-methylbutyryl base] pyrrolidine-2 (R)-yl] boric acid (PT-100).

In one aspect of the invention, the DPP-IV inhibitor is GSK-823093.

In one aspect of the invention, the DPP-IV inhibitor is PSN-9301.

In one aspect of the invention, the DPP-IV inhibitor is T-6666.

In one aspect of the invention, the DPP-IV inhibitor is SYR-322 (A Gelieting).

In one aspect of the invention, the DPP-IV inhibitor is SYR-619.

In one aspect of the invention, the DPP-IV inhibitor is CR-14023.

In one aspect of the invention, the DPP-IV inhibitor is CR-14025.

In one aspect of the invention, the DPP-IV inhibitor is CR-14240.

In one aspect of the invention, the DPP-IV inhibitor is CR-13651.

In one aspect of the invention, the DPP-IV inhibitor is NNC-72-2138.

In one aspect of the invention, the DPP-IV inhibitor is NN-7201.

In one aspect of the invention, the DPP-IV inhibitor is PHX-1149.

In one aspect of the invention, the DPP-IV inhibitor is PHX-1004.

In one aspect of the invention, the DPP-IV inhibitor is SNT-189379.

In one aspect of the invention, the DPP-IV inhibitor is GRC-8087.

In one aspect of the invention, the DPP-IV inhibitor is PT-630.

In one aspect of the invention, the DPP-IV inhibitor is SK-0403.

In one aspect of the invention, the DPP-IV inhibitor is GSK-825964.

In one aspect of the invention, the DPP-IV inhibitor is TS-021.

In one aspect of the invention, the DPP-IV inhibitor is GRC-8200.

In one aspect of the invention, the DPP-IV inhibitor is GRC-8116.

In one aspect of the invention, the DPP-IV inhibitor is FE107542.

In one aspect of the invention, the DPP-IV inhibitor is (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1,2,4] triazol [4,3-a] pyrazines-7 (8H)-yl]-1-(2,4, the 5-trifluorophenyl) fourth-2-amine.

In one aspect of the invention, the DPP-IV inhibitor is a sitagliptin.

In one aspect of the invention, the DPP-IV inhibitor is Januvia ^TM(sitagliptin phosphate).

In one aspect of the invention, the DPP-IV inhibitor is (3R)-4-[(3R)-3-amino-4-(2,4, the 5-trifluorophenyl) bytyry]-3-(2,2, the 2-trifluoroethyl)-1,4-Diazesuberane-2-ketone.

In one aspect of the invention, the DPP-IV inhibitor is selected from the right hurdle of table D.Each indivedual DPP-IV inhibitor of clearly containing the right hurdle of table D all are independent embodiment within the scope of the present invention.

In one aspect of the invention, the DPP-IV inhibitor selects the selected any chemical compound group in the right hurdle of Free Surface D.

In one aspect of the invention, the DPP-IV inhibitor is formula (XIX) chemical compound.

In one aspect of the invention, the DPP-IV inhibitor is formula (XX) chemical compound.

In one aspect of the invention, the DPP-IV inhibitor is formula (XXI) chemical compound.

In one aspect of the invention, the DPP-IV inhibitor is formula (XXII) chemical compound.

In one aspect of the invention, the DPP-IV inhibitor is the chemical compound that is selected from S1 group, T1 group, V1 group or V2 group.

In one aspect of the invention, the chemical compound that is disclosed in DPP-IV inhibitor and the international application case PCT/US02/21349 number (open with WO03/004498) is identical.

In one aspect of the invention, the chemical compound that is disclosed in DPP-IV inhibitor and the international application case PCT/EP99/09708 number (open with WO00/34241) is identical.

In one aspect of the invention, the chemical compound that is disclosed in DPP-IV inhibitor and the international application case PCT/US01/07151 number (open with WO01/68603) is identical.

In one aspect of the invention, the chemical compound that is disclosed in DPP-IV inhibitor and the international application case PCT/US2004/042209 number (open with WO 2005/095381) is identical.

In one aspect of the invention, the DPP-IV inhibitor has less than about 10 μ M, less than about 1 μ M, less than about 100nM, less than about 75nM, less than about 50nM, less than about 25nM, less than about 20nM, less than about 15nM, less than about 10nM, less than about 5nM, less than about 4nM, less than about 3nM, less than about 2nM or less than the IC of about 1nM ₅₀In certain embodiments, the DPP-IV inhibitor has less than about 50nM, less than about 25nM, less than about 20nM, less than about 15nM, less than about 10nM, less than about 5nM, less than about 4nM, less than about 3nM, less than about 2nM or less than the IC of about 1nM ₅₀

In one aspect of the invention, the DPP-IV inhibitor is a selective DPP-IV inhibitors, wherein said selective DPP-IV inhibitors has human plasma DPP-IV and is better than among PPCE, DPP-II, DPP-8 and the DPP-9 one or more at least about 10 times selectivity, and be at least about 100 times in specific embodiment, and in embodiment more specifically, be at least about 1000 times.

In one aspect of the invention, the DPP-IV inhibitor is a micromolecule.

In one aspect of the invention, DPP-IV inhibitor tool per os activity.

In one aspect of the invention, the DPP-IV inhibitor is the inhibitor of human DPP-IV.

In one aspect of the invention, can from any embodiment of the present invention, get rid of any or more than one DPP-IV inhibitor.

The combination of GPR119 agonist and DPP-IV inhibitor

As an illustration and and unrestricted, can be by from hurdle, a table D left side, selecting the GPR119 agonist and from the right hurdle of table D, selecting the DPP-IV inhibitor that exemplary combination according to GPR119 agonist of the present invention and DPP-IV inhibitor is provided.Clearly contain by from hurdle, a table D left side, selecting the GPR119 agonist and from the right hurdle of table D, selecting GPR119 agonist that the DPP-IV inhibitor provides and each indivedual combination of DPP-IV inhibitor all are within the scope of the present invention independent embodiment.

Table D

In addition, chemical compound of the present invention (comprising person described in the table D) is contained all its pharmaceutically acceptable salt, solvate and hydrate.For example referring to Burger people (1977) such as (Berge), medical science magazine (Journal ofPharmaceutical Sciences) 66:1-19; With the solid polymorphism of medicine (Polymorphism in PharmaceuticalSolids) (1999), Bu Lidun (Brittain) compiles, and Marcel moral Kerr Corp (Marcel Dekker, Inc.); Being incorporated herein by reference in full of the disclosure of described each file.

Compositions/composite and Therapeutic Method

Can use in the affiliated field well-known technology to allocate with the GPR119 agonist of DPP-IV inhibitor combination (and comprise with above-mentioned GPR119 agonist and DPP-IV inhibitor the relevant combination treatment of combination) according to circumstances to become medical composition used according to the invention and medicine according to of the present invention.Suitable composite depends on selected dosing way.

About therapy of the present invention (promptly with relevant with the GPR119 agonist of DPP-IV inhibitor combination according to circumstances therapy and comprise and above-mentioned GPR119 agonist and the relevant combination treatment of DPP-IV inhibitor), according to chemical compound of the present invention can any suitable mode throw and.Suitable dosing way comprises per os, per nasal, per rectum, through mucous membrane, percutaneous or the enteral dispensing of using known method in the affiliated field; Without the intestinal transmission, it comprises intramuscular, subcutaneous, intraspinal injection, and in the sheath, directly in the ventricle, (suction) or intraocular injection in the intravenous, intraperitoneal, intranasal, lung.Other suitable dosing way is aerosol and storage tank formula composite.The sustained releasing type composite (especially storage tank formula) of clearly containing medicine of the present invention.In some preferred embodiment, chemical compound according to the present invention be oral administration with.Chemical compound according to the present invention can be made into solid or liquid form, for example tablet, capsule, powder, syrup, elixir or the like, aerosol, sterile solution, suspension or emulsion or the like.In certain embodiments, one or both in GPR119 agonist and the DPP-IV inhibitor are oral administration with.

Except that solid tablet and capsule composite, oral composite also may be the form of aqueous solution and suspension.Described aqueous solution and suspension can be prepared by sterilized powder or granule.Can be in water, Polyethylene Glycol, propylene glycol, ethanol, Semen Maydis oil, Oleum Gossypii semen, Oleum Arachidis hypogaeae semen, Oleum sesami, benzylalcohol, sodium chloride and/or various buffer with compound dissolution.Well-known other adjuvant in the affiliated field.

To recognize that GPR119 agonist and DPP-IV inhibitor can the combination preparation form present, with simultaneously, be used for the treatment of respectively or successively or prevent to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and be used to increase the bone mass of individuality.Described combination preparation can be (for example) double pack form.

Therefore will further recognize, the product that comprises GPR119 agonist and DPP-IV inhibitor or be made up of GPR119 agonist and DPP-IV inhibitor basically that is the combination preparation form is contained in the present invention, the bone mass that it is used for the treatment of or prevent to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and be used to increase individuality simultaneously, respectively or successively.

Can be by GPR119 agonist and DPP-IV inhibitor be mixed with pharmaceutically acceptable as described herein supporting agent, excipient, binding agent, diluent etc. jointly or independently, and, prepare the combination of the present invention that comprises GPR119 agonist and DPP-IV inhibitor or form by GPR119 agonist and DPP-IV inhibitor basically with medical composition form per os or non-oral administration and described mixture.

Therefore will further recognize, GPR119 agonist and DPP-IV inhibitor or medical composition separately dosage form or single dosage form is thrown and.

Further recognize, when GPR119 agonist and DPP-IV inhibitor are independent dosage form, GPR119 agonist and DPP-IV inhibitor can different approaches throw with.

Can come individually or prepare the medical composition of GPR119 agonist and DPP-IV inhibitor by well-known method in the affiliated field (for example, by routine mixing, dissolving, pelletize, dragee manufacturing, fine grinding, emulsifying, capsule envelope, embedding, freeze-dry process or spray drying) with compound mode.

Can use one or more physiologys to go up acceptable supporting agent and allocate medical composition used according to the invention in a usual manner, described supporting agent comprises excipient and auxiliary agent, and its assistance is processed as pharmaceutically spendable preparation with reactive compound.The pharmaceutically acceptable supporting agent that the those skilled in the art can obtain to be fit to is [for example referring to Lei Mingdun: the science of pharmacy and enforcement (Remington:The Science and Practice of Pharmacy), (Jie Naluo people such as (Gennaro) volume), the 20th edition, 2000, (the Lippincott Williams ﹠amp of Donald Lippincott WILLIAMS-DARLING Ton Louis Wilkins publishing company; Wilkins); With medical excipient handbook (Handbook of Pharmaceutical Excipients) (people such as (Rowe) sieve volume), the 4th edition, 2003, medical publishing house (Pharmaceutical Press); It is disclosure be incorporated herein by reference in full separately].Suitable composite depends on selected dosing way.Term " supporting agent " material or " excipient " material be any material of expression itself and nontherapeutic agent in this article, it is as supporting agent and/or diluent and/or adjuvant or mediator, to be used for to individuality transmission therapeutic agent or to add medical composition to improve its processing or storage characteristics or permission or to help the unit dose formation of compositions to be suitable for oral discontinuous article (for example capsule or tablet).As an illustration and and unrestricted, excipient can comprise diluent, disintegrating agent, binding agent, sticker, wetting agent, polymer, lubricant, antiseize paste, through add with the material that covers or offsets disagreeable taste or abnormal smells from the patient, spice, dyestuff, aromatic and through adding to improve the material of compositions outward appearance.Acceptable excipient comprises stearic acid, magnesium stearate, magnesium oxide, phosphoric acid and vitriolic sodium salt and calcium salt, magnesium carbonate, Talcum, gelatin, arabic gum, sodium alginate, pectin, dextrin, mannitol, Sorbitol, lactose, sucrose, starch, gelatin, cellulosic material (for example cellulose esters of alkanoic acid and cellulose Arrcostab), low melt wax, cocoa butter or powder, polymer (polyethylene-ketopyrrolidine for example, polyvinyl alcohol and Polyethylene Glycol) and other pharmaceutically acceptable material.The component of medical composition can through capsule envelope or film-making with convenient throw with.

Pharmaceutically acceptable being meant about compositions, composite, stability, patient's acceptance and biological usability can be that the patient accepts and can be according to the physical/chemical viewpoint according to pharmacology/toxicological viewpoint and make those character and/or the material that Pharmaceutical Chemist is accepted.

About the combinations thereof therapy, when GPR119 agonist and DPP-IV inhibitor were independent dosage form, it was identical with the pharmaceutically acceptable supporting agent that is used for DPP-IV inhibitor composite to should be appreciated that the pharmaceutically acceptable supporting agent that is used for GPR119 agonist composite does not need.

Dragee nuclear has suitable coating.With regard to this purpose, can use priming (it can contain arabic gum, Talcum, polyvinylpyrrolidone, carbomer gel (carbopol gel), Polyethylene Glycol and/or titanium dioxide according to circumstances), lacquer solution and suitable organic solvent or solvent mixture.Can in tablet or dragee coating, add stain or pigment, to differentiate or to characterize different active compound doses combinations.

But the medical composition that per os uses comprises the push style capsule of being made by gelatin, and the soft seal capsule of being made by gelatin and plasticizer (for example glycerol or Sorbitol).Described push style capsule can contain active component and filler (for example lactose), binding agent (for example starch) and/or lubricant (for example Talcum or magnesium stearate) and the mixture of stabilizing agent according to circumstances.In soft capsule, can or be suspended in reactive compound dissolving and be fit in the liquid, for example fatty oil, liquid paraffin, liquid macrogol, polyoxyethylene ether Oleum Ricini (cremophor), Kapp nurse (capmul), in or the single, double or triglyceride of long-chain.Also can in these composites, add stabilizing agent.

In addition, can use sustained release system to transmit the combination of GPR119 agonist and GPR119 agonist and DPP-IV inhibitor.Various sustained-release material are determined and are that the those skilled in the art is well-known.Especially preferred continuous release tablet or capsule.For instance, can use the time-delay material, for example glyceryl monostearate or distearin.Also can be coated with coating to dosage form, be used for controlled release with the formation osmotic therapeutic tablets by the technology described in the United States Patent (USP) the 4th, 256, No. 108, the 4th, 166, No. 452 and the 4th, 265, No. 874.

One or more other medicine and pharmacology or physiology go up acceptable chemical compound and throw and or provide alone or in combination clearly to contain therapy of the present invention (promptly with relevant with the GPR119 agonist of DPP-IV inhibitor combination according to circumstances therapy and comprise and above-mentioned GPR119 agonist and the relevant combination treatment of DPP-IV inhibitor).In one aspect of the invention, it is not that the GPR119 agonist neither the DPP-IV inhibitor that described other medicine and pharmacology or physiology go up acceptable chemical compound.In one aspect of the invention, it is medical agent that described other medicine and pharmacology or physiology go up acceptable chemical compound, and it is selected from by calcium, vitamin D, estrogen, tibolone (tibolone), selective estrogen receptor modulators (SERM; Lei Luoxifen (raloxifene) for example; tamoxifen (tamoxifen)); diphosphonate (etidronate (etidronate) for example; fosamax (alendronate); Risedronate (risedronate)); calcitonin (calcitonin); 1 'alpha '-hydroxylation metabolite of vitamin D; fluoride; thiadiazide (thiazide); anabolic steroid; ipriflavone (ipriflavone); vitamin K; parathyroid hormone (PTH); strontium; his spit of fland (statin); osteoprotegerin (osteoprotererin); the EP4 receptor selective agonists; the group that 2 type Cannabined receptor (CB2) selective agonists and p38MAP inhibitors of kinases are formed.(for example referring to World Health Organization's technical report book series 921 (World HealthOrganization Technical Report Series 921) (2003), osteoporosis prevention and processing (Preventionand Management of Osteoporosis).)

In combination treatment according to the present invention, according to GPR119 agonist of the present invention and according to DPP-IV inhibitor of the present invention can throw simultaneously with or with the interval that separates throw with.Throw at the same time and the time, GPR119 agonist and DPP-IV inhibitor can be included in the single medical composition or include in the independent compositions, for example, the GPR119 agonist is included in a kind of compositions and the DPP-IV inhibitor is included in the another kind of compositions.In these compositionss each can be allocated with usual excipients, diluent or supporting agent, and is pressed into tablet, or is allocated as elixir or solution; And make sustained release forms or the like.GPR119 agonist and DPP-IV inhibitor can by different approaches throw with.For instance, the GPR119 agonist can via the tablet oral administration with and the DPP-IV inhibitor can via suck to throw with.

Throw respectively and the time, the GPR119 agonist according to the present invention of treatment effective dose and DPP-IV inhibitor be with different time-histories throw with.A kind of material can before another kind of material, throw with, as long as the time between twice dispensing treatment effective time at interval within.Treatment effective time be at interval start from (a) GPR119 agonist or (b) a kind of in the DPP-IV inhibitor throw with individual and terminate in one period of (a) and the beneficial effect time limit of (b) combined therapy.

On the one hand, the invention provides a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention, or is made up of a certain amount of GPR119 agonist according to the present invention basically.On the one hand, the invention provides a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and at least a pharmaceutically acceptable supporting agent, or is made up of according to GPR119 agonist of the present invention and at least a pharmaceutically acceptable supporting agent a certain amount of basically.

On the one hand, the invention provides a kind of combination, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention a certain amount of basically.On the one hand, the invention provides a kind of medicine combination, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention a certain amount of basically.

On the one hand, the invention provides a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention, or is made up of a certain amount of GPR119 agonist according to the present invention basically.On the one hand, the invention provides a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and at least a pharmaceutically acceptable supporting agent, or is made up of according to GPR119 agonist of the present invention and at least a pharmaceutically acceptable supporting agent a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist is enough to provide treatment or prevention to be characterised in that condition of illness (for example osteoporosis) that hangs down bone mass and/or the effect that increases individual bone mass.

On the one hand, the invention provides a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention a certain amount of basically.On the one hand, the invention provides a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist and DPP-IV inhibitor is enough to provide treatment or prevention to be characterised in that condition of illness (for example osteoporosis) that hangs down bone mass and/or the effect that increases individual bone mass.

On the one hand, the invention provides a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention a certain amount of basically.On the one hand, the invention provides a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist and DPP-IV inhibitor is enough to provide treatment or prevention to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and/or increases the effect of individual bone mass, and the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is characterised in that the condition of illness (for example osteoporosis) of low bone mass for treatment or prevention and/or increases the individual bone mass ineffective in treatment.

On the one hand, the invention provides a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention a certain amount of basically.On the one hand, the invention provides a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist and DPP-IV inhibitor is enough to provide treatment or prevention to be characterised in that condition of illness (for example osteoporosis) that hangs down bone mass and/or the effect that increases individual bone mass, and wherein said effect is a synergism.

On the one hand, the present invention relates to a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention a certain amount of basically.On the one hand, the present invention relates to a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist and DPP-IV inhibitor is enough to provide treatment or prevention to be characterised in that condition of illness (for example osteoporosis) that hangs down bone mass and/or the effect that increases individual bone mass, wherein said effect is a synergism, and the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is ineffective on treating for treating or prevent to be characterised in that condition of illness (for example osteoporosis) that hangs down bone mass and/or the bone mass that increases individuality.

On the one hand, the present invention relates to a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention a certain amount of basically.On the one hand, the present invention relates to a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist and DPP-IV inhibitor is enough to provide treatment or prevention to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and/or increases the effect of individual bone mass, wherein effect that is provided separately greater than the GPR119 agonist by described amount by the effect that combination provided of the DPP-IV inhibitor of the GPR119 agonist of described amount and described amount and the effect that provided separately by the DPP-IV inhibitor of described amount.

On the one hand, the invention provides a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention, or is made up of a certain amount of GPR119 agonist according to the present invention basically.On the one hand, the invention provides a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and at least a pharmaceutically acceptable supporting agent, or is made up of according to GPR119 agonist of the present invention and at least a pharmaceutically acceptable supporting agent a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist is enough to provide the effect that increases individual GIP content.

On the one hand, the invention provides a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention a certain amount of basically.On the one hand, the invention provides a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist and DPP-IV inhibitor is enough to provide the effect that increases individual GIP content.

On the one hand, the invention provides a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention a certain amount of basically.On the one hand, the invention provides a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist and DPP-IV inhibitor is enough to the effect that increases individual GIP content is provided, and the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is ineffective in treatment for increasing individual GIP content.

On the one hand, the invention provides a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention a certain amount of basically.On the one hand, the invention provides a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist and DPP-IV inhibitor is enough to the effect that increases individual GIP content is provided, and wherein said effect is a synergism.

On the one hand, the present invention relates to a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention a certain amount of basically.On the one hand, the present invention relates to a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist and DPP-IV inhibitor is enough to provide the effect that increases individual GIP content, wherein said effect is a synergism, and the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is ineffective in treatment for increasing individual GIP content.

On the one hand, the present invention relates to a kind of compositions, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination according to DPP-IV inhibitor of the present invention a certain amount of basically.On the one hand, the present invention relates to a kind of medical composition, it comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of combination and at least a pharmaceutically acceptable supporting agent according to DPP-IV inhibitor of the present invention a certain amount of basically.The present invention also relates to the dosage form of a kind of described compositions or described medical composition, wherein the amount of GPR119 agonist and DPP-IV inhibitor is enough to provide the effect that increases individual GIP content, wherein effect that is provided separately greater than the GPR119 agonist by described amount by the effect that combination provided of the DPP-IV inhibitor of the GPR119 agonist of described amount and described amount and the effect that provided separately by the DPP-IV inhibitor of described amount.

Be applicable to that the medical composition among the present invention comprises the composition of active components that contains the amount that can realize its intended purposes.In certain embodiments, should be appreciated that the bone mass that medical composition of the present invention can be used for treating or prevent to be characterised in that the condition of illness (for example osteoporosis) of low bone mass or is used to increase individuality.The condition of illness that is characterised in that low bone mass is according to the present invention.In certain embodiments, should be appreciated that medical composition of the present invention can be used for increasing individual GIP content.About the present invention, to be enough to realize according to the amount of the combination of the amount of the GPR119 agonist of intended purposes of the present invention or GPR119 agonist and DPP-IV inhibitor determine be in fully in one of ordinary skill in the art's the limit of power, especially according to the detailed disclosure that is provided herein.

The data that obtain from animal research (including but not limited to use mice, rat, rabbit, pig and non-human primate's research) can be used for allocating the dosage range that is used for the mankind.In general, the those skilled in the art understands how the in vivo data that obtained in the animal model system are extrapolated to another system (for example human).In some cases, these extrapolations can only be carried out according to the body weight contrast of described animal model and another system (for example human); Under other situation, these extrapolations then are not to carry out according to body weight simply, but include multiple factor in.Representative factor comprises patient's type, age, body weight, sex, diet and medical science condition of illness; Severity of disease; Dosing way; The pharmacology considers, the for example activity of used particular compound, effect, pharmacodynamics and toxicology overview, whether use drug delivery system, whether treat or prevent, or except that The compounds of this invention and as the part of drug regimen, whether throw and other reactive compound over against acute or chronic disease state.Select to treat the dosage regimen of morbid state with chemical compound of the present invention and/or compositions according to aforesaid multiple factor.Therefore, used actual dosage regimen can extensively change and therefore may depart from preferred dosage regimen, and those skilled in the art will realize that dosage outside these typical ranges and dosage regimen can be through tests, and can be used in due course in the method for the present invention.

A kind of exemplary animal model system is rat ovary excision (OVX) bone forfeiture model.Ovary through the rat of excision be fabulous clinical before animal model, it can accurately simulate estrogen loss human skeleton's the important clinical feature and the reaction of therapeutic agent.In this model, when the bone forfeiture relevant with ovariectomy partially or completely prevented, realize therapeutic efficiency.(for example referring to Bo Lage people such as (Bollag), molecular cell endocrinology (Mol Cell Endocrinol) (2001) 177:35-41; And lucky people such as (Jee), muscle skeleton neuron neuron interaction magazine (J Musculoskel NeuronInteract) (2001) 1:193-207.) in certain embodiments, when the bone relevant with ovariectomy forfeiture obtains prevention, prevention, prevention, prevention, prevention, prevention, prevention, prevention, prevention, prevention, prevention, prevention at least about 95% at least about 90% at least about 85% at least about 80% at least about 75% at least about 70% at least about 60% at least about 50% at least about 40% at least about 30% at least about 20% at least about 10% or 100% prevention, realize therapeutic efficiency.

Another kind of exemplary animal model system is the mice that blood GIP content increases behind the glucose counteracting toxic substances.In certain embodiments, blood GIP content is blood plasma GIP content.In certain embodiments, GIP content is glucose dependent/non-dependent GIP content.In certain embodiments, GIP content is glucose dependency GIP content.In certain embodiments, GIP is total GIP.In certain embodiments, total GIP is to use central authorities or the analysis of C-terminal guidance quality to measure.In certain embodiments, GIP is biological activity GIP.In certain embodiments, biological activity GIP is to use the N-terminal specificity analyses to measure.In certain embodiments, biological activity GIP has the osteoplastic activity of promotion.In certain embodiments, when blood GIP content increase at least about 10%, at least about 25%, at least about 50%, at least about 100%, at least about 150%, at least about 200%, at least about 300%, at least about 400% or at least about 500% the time, realize therapeutic efficiency.

Scalable dosage and interval are to provide the expection therapeutical effect.Should be appreciated that, will look following factor according to the definite dosage of GPR119 agonist of the present invention or DPP-IV inhibitor and change: the seriousness of the combination of GPR119 agonist, GPR119 agonist and DPP-IV inhibitor, its effectiveness, dispensing pattern, patient's age and body weight and desire treatment condition of illness.Definite composite, dosing way and dosage can be selected according to status of patient by indivedual doctors.As an illustration and and unrestricted, according to the amount of the amount of GPR119 agonist of the present invention and/or DPP-IV inhibitor less than about 0.001 milligram of per kilogram of body weight, less than about 0.005 milligram of per kilogram of body weight, less than about 0.01 milligram of per kilogram of body weight, less than about 0.05 milligram of per kilogram of body weight, less than about 0.1 milligram of per kilogram of body weight, less than about 0.5 milligram of per kilogram of body weight, less than about 1 milligram of per kilogram of body weight, less than about 5 milligrams of per kilogram of body weight, less than about 10 milligrams of per kilogram of body weight, less than about 50 milligrams or of per kilogram of body weight less than about 100 milligrams of per kilogram of body weight.In certain embodiments, according to the amount of the amount of GPR119 agonist of the present invention and/or DPP-IV inhibitor less than about 0.001 milligram-100 milligrams of per kilogram of body weight, less than about 0.001 milligram-50 milligrams of per kilogram of body weight, less than about 0.001 milligram-10 milligrams of per kilogram of body weight, less than about 0.001 milligram-5 milligrams of per kilogram of body weight, less than about 0.001 milligram-1 milligram of per kilogram of body weight, less than about 0.001 milligram to 0.5 milligram of per kilogram of body weight, less than about 0.001 milligram-0.1 milligram of per kilogram of body weight, less than about 0.001 milligram-0.05 milligram of per kilogram of body weight, less than about 0.001 milligram-0.01 milligram or of per kilogram of body weight less than about 0.001 milligram-0.005 milligram of per kilogram of body weight.

The combination of clearly containing GPR119 agonist and GPR119 agonist and DPP-IV inhibitor can be used for preventing individual bone forfeiture method (for example prevention of osteoporosis amount reduce method), suppress individual bone forfeiture method (for example suppressing the method that bone mass reduces), keep the method for individual bone mass and promote in the individual osteoplastic method (for example increasing the method for bone mass).

But every day or regular throw with preferred dose scope with a certain amount of GPR119 agonist of realizing required result be per kilogram body quality 0.001-100 milligram (mpk).Other preferred dose scope is 0.001 milligram-30 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-10 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-3.0 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-1.0 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-0.3 milligram of a per kilogram body quality.Other preferred dose scope is 0.001 milligram-0.1 milligram of a per kilogram body quality.Other preferred dose scope is 0.001 milligram-0.03 milligram of a per kilogram body quality.Other preferred dose scope is 0.001 milligram-0.01 milligram of a per kilogram body quality.Certainly, these every day dosage can be within one day with periodically transmit in a small amount or throw and.It should be noted that these dosage ranges are preferable range and are not intended to limit the present invention.

But be used in combination with the DPP-IV inhibitor so that described combination every day or regular throw with preferred dose scope with a certain amount of GPR119 agonist of realizing required result be 0.001 milligram-100 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-30 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-10 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-3.0 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-1.0 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-0.3 milligram of a per kilogram body quality.Other preferred dose scope is 0.001 milligram-0.1 milligram of a per kilogram body quality.Other preferred dose scope is 0.001 milligram-0.03 milligram of a per kilogram body quality.Other preferred dose scope is 0.001 milligram-0.01 milligram of a per kilogram body quality.Certainly, these every day dosage can be within one day with periodically transmit in a small amount or throw and.It should be noted that these dosage ranges are preferable range and are not intended to limit the present invention.

But be used in combination with the GPR119 agonist so that described combination every day or regular throw with preferred dose scope with a certain amount of DPP-IV inhibitor of realizing required result be 0.001 milligram-100 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-30 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-10 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-3.0 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-1.0 milligrams of per kilogram body qualities.Other preferred dose scope is 0.001 milligram-0.3 milligram of a per kilogram body quality.Other preferred dose scope is 0.001 milligram-0.1 milligram of a per kilogram body quality.Other preferred dose scope is 0.001 milligram-0.03 milligram of a per kilogram body quality.Other preferred dose scope is 0.001 milligram-0.01 milligram of a per kilogram body quality.Certainly, these every day dosage can be within one day with periodically transmit in a small amount or throw and.It should be noted that these dosage ranges are preferable range and are not intended to limit the present invention.

But clearly contain GPR119 agonist or GPR119 agonist and DPP-IV inhibitor combination every day or regular throw with to realize that individual GIP content increases.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content increases.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with realizing that individual blood (for example blood plasma or serum) GIP content increases, its be individual normal blood GIP content (for example normal blood plasma GIP content before the meal or between normal blood plasma GIP content before the meal and the blood plasma GIP content between the blood plasma GIP content after the meal) or before treatment individual blood GIP content 110% to 1000%, 110% to 900%, 110% to 800%, 110% to 700%, 110% to 600%, 110% to 500%, 110% to 400%, 110% to 300%, 110% to 200% or 110% to 150%.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with realizing that individual blood (for example blood plasma or serum) GIP content increases, its be individual normal blood GIP content (for example normal blood plasma GIP content before the meal or between normal blood plasma GIP content before the meal and the blood plasma GIP content between the blood plasma GIP content after the meal) or before treatment individual blood GIP content 150% to 1000%, 150% to 900%, 150% to 800%, 150% to 700%, 150% to 600%, 150% to 500%, 150% to 400%, 150% to 300% or 150% to 200%.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with realizing that individual blood (for example blood plasma or serum) GIP content increases, its be individual normal blood GIP content (for example normal blood plasma GIP content before the meal or between normal blood plasma GIP content before the meal and the blood plasma GIP content between the blood plasma GIP content after the meal) or before treatment individual blood GIP content 200% to 1000%, 200% to 900%, 200% to 800%, 200% to 700%, 200% to 600%, 200% to 500%, 200% to 400% or 200% to 300%.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with realizing that individual blood (for example blood plasma or serum) GIP content increases, its be individual normal blood GIP content (for example normal blood plasma GIP content before the meal or between normal blood plasma GIP content before the meal and the blood plasma GIP content between the blood plasma GIP content after the meal) or before treatment individual blood GIP content 250% to 1000%, 250% to 900%, 250% to 800%, 250% to 700%, 250% to 600%, 250% to 500%, 250% to 400% or 250% to 300%.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with realizing that individual blood (for example blood plasma or serum) GIP content increases, its be individual normal blood GIP content (for example normal blood plasma GIP content before the meal or between normal blood plasma GIP content before the meal and the blood plasma GIP content between the blood plasma GIP content after the meal) or before treatment individual blood GIP content 300% to 1000%, 300% to 900%, 300% to 800%, 300% to 700%, 300% to 600%, 300% to 500% or 300% to 400%.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with realizing that individual blood (for example blood plasma or serum) GIP content increases, its be individual normal blood GIP content (for example normal blood plasma GIP content before the meal or between normal blood plasma GIP content before the meal and the blood plasma GIP content between the blood plasma GIP content after the meal) or before treatment individual blood GIP content 400% to 1000%, 400% to 900%, 400% to 800%, 400% to 700%, 400% to 600% or 400% to 500%.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with realizing that individual blood (for example blood plasma or serum) GIP content increases, its be individual normal blood GIP content (for example normal blood plasma GIP content before the meal or between normal blood plasma GIP content before the meal and the blood plasma GIP content between the blood plasma GIP content after the meal) or before treatment individual blood GIP content 500% to 1000%, 500% to 900%, 500% to 800%, 500% to 700% or 500% to 600%.In certain embodiments, blood (for example blood plasma or serum) GIP content is the total GIP content of blood (for example blood plasma or serum).In certain embodiments, blood (for example blood plasma or serum) GIP content is blood (for example blood plasma or serum) biological activity (activity) GIP content.The blood GIP content range that it should be noted that these increases is exemplary scope and is not intended to limit the present invention.

But clearly contain GPR119 agonist or GPR119 agonist and DPP-IV inhibitor combination every day or regular throw with to realize that individual GIP content increases.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content increases.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content is in following concentration range: 100 pg/ml (pg/ml) are to 2000 pg/ml, 100 pg/ml to 1900 pg/ml, 100 pg/ml to 1800 pg/ml, 100 pg/ml to 1700 pg/ml, 100 pg/ml to 1600 pg/ml, 100 pg/ml to 1500 pg/ml, 100 pg/ml to 1400 pg/ml, 100 pg/ml to 1300 pg/ml, 100 pg/ml to 1200 pg/ml, 100 pg/ml to 1100 pg/ml, 100 pg/ml to 1000 pg/ml, 100 pg/ml to 900 pg/ml, 100 pg/ml to 800 pg/ml, 100 pg/ml to 700 pg/ml, 100 pg/ml to 600 pg/ml, 100 pg/ml to 500 pg/ml, 100 pg/ml to 400 pg/ml, 100 pg/ml to 300 pg/ml or 100 pg/ml to 200 pg/ml.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content is in following concentration range: 200 pg/ml to 2000 pg/ml, 200 pg/ml to 1900 pg/ml, 200 pg/ml to 1800 pg/ml, 200 pg/ml to 1700 pg/ml, 200 pg/ml to 1600 pg/ml, 200 pg/ml to 1500 pg/ml, 200 pg/ml to 1400 pg/ml, 200 pg/ml to 1300 pg/ml, 200 pg/ml to 1200 pg/ml, 200 pg/ml to 1100 pg/ml, 200 pg/ml to 1000 pg/ml, 200 pg/ml to 900 pg/ml, 200 pg/ml to 800 pg/ml, 200 pg/ml to 700 pg/ml, 200 pg/ml to 600 pg/ml, 200 pg/ml to 500 pg/ml, 200 pg/ml to 400 pg/ml or 200 pg/ml to 300 pg/ml.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content is in following concentration range: 300 pg/ml to 2000 pg/ml, 300 pg/ml to 1900 pg/ml, 300 pg/ml to 1800 pg/ml, 300 pg/ml to 1700 pg/ml, 300 pg/ml to 1600 pg/ml, 300 pg/ml to 1500 pg/ml, 300 pg/ml to 1400 pg/ml, 300 pg/ml to 1300 pg/ml, 300 pg/ml to 1200 pg/ml, 300 pg/ml to 1100 pg/ml, 300 pg/ml to 1000 pg/ml, 300 pg/ml to 900 pg/ml, 300 pg/ml to 800 pg/ml, 300 pg/ml to 700 pg/ml, 300 pg/ml to 600 pg/ml, 300 pg/ml to 500 pg/ml or 300 pg/ml to 400 pg/ml.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content is in following concentration range: 400 pg/ml to 2000 pg/ml, 400 pg/ml to 1900 pg/ml, 400 pg/ml to 1800 pg/ml, 400 pg/ml to 1700 pg/ml, 400 pg/ml to 1600 pg/ml, 400 pg/ml to 1500 pg/ml, 400 pg/ml to 1400 pg/ml, 400 pg/ml to 1300 pg/ml, 400 pg/ml to 1200 pg/ml, 400 pg/ml to 1100 pg/ml, 400 pg/ml to 1000 pg/ml, 400 pg/ml to 900 pg/ml, 400 pg/ml to 800 pg/ml, 400 pg/ml to 700 pg/ml, 400 pg/ml to 600 pg/ml or 400 pg/ml to 500 pg/ml.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content is in following concentration range: 500 pg/ml to 2000 pg/ml, 500 pg/ml to 1900 pg/ml, 500 pg/ml to 1800 pg/ml, 500 pg/ml to 1700 pg/ml, 500 pg/ml to 1600 pg/ml, 500 pg/ml to 1500 pg/ml, 500 pg/ml to 1400 pg/ml, 500 pg/ml to 1300 pg/ml, 500 pg/ml to 1200 pg/ml, 500 pg/ml to 1100 pg/ml, 500 pg/ml to 1000 pg/ml, 500 pg/ml to 900 pg/ml, 500 pg/ml to 800 pg/ml, 500 pg/ml to 700 pg/ml or 500 pg/ml to 600 pg/ml.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content is in following concentration range: 600 pg/ml to 2000 pg/ml, 600 pg/ml to 1900 pg/ml, 600 pg/ml to 1800 pg/ml, 600 pg/ml to 1700 pg/ml, 600 pg/ml to 1600 pg/ml, 600 pg/ml to 1500 pg/ml, 600 pg/ml to 1400 pg/ml, 600 pg/ml to 1300 pg/ml, 600 pg/ml to 1200 pg/ml, 600 pg/ml to 1100 pg/ml, 600 pg/ml to 1000 pg/ml, 600 pg/ml to 900 pg/ml, 600 pg/ml to 800 pg/ml or 600 pg/ml to 700 pg/ml.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content is in following concentration range: 700 pg/ml to 2000 pg/ml, 700 pg/ml to 1900 pg/ml, 700 pg/ml to 1800 pg/ml, 700 pg/ml to 1700 pg/ml, 700 pg/ml to 1600 pg/ml, 700 pg/ml to 1500 pg/ml, 700 pg/ml to 1400 pg/ml, 700 pg/ml to 1300 pg/ml, 700 pg/ml to 1200 pg/ml, 700 pg/ml to 1100 pg/ml, 700 pg/ml to 1000 pg/ml, 700 pg/ml to 900 pg/ml or 700 pg/ml to 800 pg/ml.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content is in following concentration range: 800 pg/ml to 2000 pg/ml, 800 pg/ml to 1900 pg/ml, 800 pg/ml to 1800 pg/ml, 800 pg/ml to 1700 pg/ml, 800 pg/ml to 1600 pg/ml, 800 pg/ml to 1500 pg/ml, 800 pg/ml to 1400 pg/ml, 800 pg/ml to 1300 pg/ml, 800 pg/ml to 1200 pg/ml, 800 pg/ml to 1100 pg/ml, 800 pg/ml to 1000 pg/ml or 800 pg/ml to 900 pg/ml.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content is in following concentration range: 900 pg/ml to 2000 pg/ml, 900 pg/ml to 1900 pg/ml, 900 pg/ml to 1800 pg/ml, 900 pg/ml to 1700 pg/ml, 900 pg/ml to 1600 pg/ml, 900 pg/ml to 1500 pg/ml, 900 pg/ml to 1400 pg/ml, 900 pg/ml to 1300 pg/ml, 900 pg/ml to 1200 pg/ml, 900 pg/ml to 1100 pg/ml or 900 pg/ml to 1000 pg/ml.In certain embodiments, blood (for example blood plasma or serum) GIP content is the total GIP content of blood (for example blood plasma or serum).In certain embodiments, blood (for example blood plasma or serum) GIP content is blood (for example blood plasma or serum) biological activity (activity) GIP content.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be every day or regular throw with to realize that individual blood (for example blood plasma or serum) GIP content is in following concentration range: 1000 pg/ml to 2000 pg/ml, 1000 pg/ml to 1900 pg/ml, 1000 pg/ml to 1800 pg/ml, 1000 pg/ml to 1700 pg/ml, 1000 pg/ml to 1600 pg/ml, 1000 pg/ml to 1500 pg/ml, 1000 pg/ml to 1400 pg/ml, 1000 pg/ml to 1300 pg/ml, 1000 pg/ml to 1200 pg/ml or 1000 pg/ml to 1100 pg/ml.In certain embodiments, blood (for example blood plasma or serum) GIP content is the total GIP content of blood (for example blood plasma or serum).In certain embodiments, blood (for example blood plasma or serum) GIP content is blood (for example blood plasma or serum) biological activity (activity) GIP content.It should be noted that these blood GIP concentration range is exemplary scope and is not intended to limit the present invention.

In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor is that every day or regularity are thrown and to realize that individual GIP content increases, its mode can't cause the downward modulation or the substance downward modulation (the proteic content reduction of gip receptor) of (for example in the Thigh bone) (for example in osteoblast) gip receptor in the bone.In certain embodiments, in the bone the proteic content of gip receptor reduce less than about 90%, less than about 80%, less than about 70%, less than about 60%, less than about 50%, less than about 40%, less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5% or less than about 2.5%.In certain embodiments, in the bone the proteic content of gip receptor reduce less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5% or less than about 2.5%.In certain embodiments, in the bone the proteic content of gip receptor reduce less than about 10%, less than about 5% or less than about 2.5%.In certain embodiments, the proteic content of gip receptor does not reduce in the bone.In certain embodiments, blood (for example blood plasma or serum) GIP content is the total GIP content of blood (for example blood plasma or serum).In certain embodiments, blood (for example blood plasma or serum) GIP content is blood (for example blood plasma or serum) biological activity (activity) GIP content.Become known for assessing the suitable animal model (for example mice, rat) of GIP content in the affiliated field to the influence of gip receptor downward modulation in the bone.The those skilled in the art becomes known for measuring the method for the downward modulation of gip receptor in the bone and it and comprises that (for example) use the western blot (Western blot) at the antibody of gip receptor.For example referring to thanking people such as (Xie), bone (Bone), 2007.

In certain embodiments, the GPR119 agonist is the GPR119 partial agonist.

In certain embodiments, the GPR119 agonist is non-endogenous GPR119 agonist.

In certain embodiments, the throwing of the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be oral.

In some embodiment relevant with the combination of GPR119 agonist and DPP-IV inhibitor, GPR119 agonist and DPP-IV inhibitor be with independent dosage form or single dosage form throw with.

In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be with realize individual GIP with pulsation or the mode that raises of interim mode throw with.The pulsation of GIP or interim rising will represent that blood (for example blood plasma or serum) GIP content is elevated to peak content and returns described baseline content from baseline content at least once a day.In certain embodiments, the baseline content of blood plasma GIP is blood plasma GIP content before the meal normally approximately.In certain embodiments, the baseline content of blood plasma GIP is between blood plasma GIP content and after the meal between the blood plasma GIP content before the meal normally.The those skilled in the art will know the pulsation or interim rising of how to realize individual GIP.In certain embodiments, pulsation or interim raise be by so that the GIP that first predose produced raise act on throw with subsequent dose before the combination of throwing with GPR119 agonist or GPR119 agonist and DPP-IV inhibitor of the mode of full consumption realize.In certain embodiments, the pulsation of GIP or interim the rising are to realize with the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor by (for example in the back of ingesting) throwing when plasma glucose content raises.In certain embodiments, blood (for example blood plasma or serum) GIP content is the total GIP content of blood (for example blood plasma or serum).In certain embodiments, blood (for example blood plasma or serum) GIP content is blood (for example blood plasma or serum) biological activity (activity) GIP content.

Clearly containing administration time at interval can be relevant with ingest time.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be before ingesting, during or throw afterwards with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be before ingesting, throw with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be ingest preceding 120 minutes or 120 minutes with interior throwing with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be ingest preceding 90 minutes or 90 minutes with interior throwing with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be ingest preceding 60 minutes or 60 minutes with interior throwing with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be ingest preceding 30 minutes or 30 minutes with interior throwing with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be ingest preceding 15 minutes or 15 minutes with interior throwing with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be during ingesting, throw with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be throw in the back of ingesting with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be ingest back 120 minutes or 120 minutes with interior throwing with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be ingest back 90 minutes or 90 minutes with interior throwing with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be ingest back 60 minutes or 60 minutes with interior throwing with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be ingest back 30 minutes or 30 minutes with interior throwing with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be ingest back 15 minutes or 15 minutes with interior throwing with.It should be noted that these intervals are exemplary intervals and are not intended to limit the present invention.In certain embodiments, dispensing is oral.In some embodiment relevant with the combination of GPR119 agonist and DPP-IV inhibitor, GPR119 agonist and DPP-IV inhibitor be with independent dosage form or with single dosage form throw with.In certain embodiments, ingesting is to ingest every day, for example breakfast, lunch, dinner or the like.In certain embodiments, ingesting is every day by the rule scheduling to ingest for example breakfast, lunch, dinner or the like.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be once or ingest once above every day (for example breakfast, lunch, dinner or the like) before, during or throw afterwards with.In certain embodiments, the combination of GPR119 agonist or GPR119 agonist and DPP-IV inhibitor be once or ingest the every day of arranging the time by rule once (for example breakfast, lunch, dinner or the like) before, during or throw afterwards with.

Term " pharmaceutically acceptable salt " is meant by pharmaceutically acceptable nontoxic alkali or the prepared salt of acid (comprising inorganic base or organic base and mineral acid or organic acid).Salt derived from inorganic base comprises aluminum salt, ammonium salt, calcium salt, mantoquita, iron salt, ferrous salt, lithium salts, magnesium salt, manganese salt, manganous salt, potassium salt, sodium salt, zinc salt or the like.In certain embodiments, the salt derived from inorganic base comprises ammonium salt, calcium salt, magnesium salt, potassium salt and sodium salt.The salt of solid form can more than one crystal structure exist, and also can exist by hydrate forms.The salt that comprises following each alkali derived from the salt of pharmaceutically acceptable organic nontoxic alkali: primary amine, secondary amine and tertiary amine, be substituted amine (comprising the naturally occurring amine that is substituted), cyclammonium and deacidite, arginine for example, betanin, caffeine, choline, N, N '-dibenzyl-ethylenediamin, diethylamine, the 2-DEAE diethylaminoethanol, the 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethyl-morpholine, N-ethylpiperidine, glucamine (glucamine), glycosamine (glucosamine), histidine, Hai Baming (hydrabamine), 2-aminopropane., lysine, meglumine (methylglucamine), morpholine, piperazine, piperidines, polyamino resin, procaine (procaine), purine, theobromine, triethylamine, trimethylamine, tripropyl amine (TPA), trometamol (tromethamine) or the like.

When chemical compound of the present invention is alkalescence, can prepare salt by pharmaceutically acceptable non-toxic acid (comprising inorganic and organic acid).These acid comprise acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethane sulfonic acid, fumaric acid, gluconic acid, glutamic acid, hydrobromic acid, hydrochloric acid, hydroxyethylsulfonic acid., lactic acid, maleic acid, malic acid, mandelic acid, Loprazolam, glactaric acid, nitric acid, pamoic acid, pantothenic acid, phosphoric acid, succinic acid, sulphuric acid, tartaric acid, p-methyl benzenesulfonic acid or the like.In certain embodiments, these acid comprise citric acid, hydrobromic acid, hydrochloric acid, maleic acid, phosphoric acid, sulphuric acid, fumaric acid and tartaric acid.

Can individually regulate dosage and interval with provide realize the expection therapeutical effect according to GPR119 agonist of the present invention and/or according to the plasma content of DPP-IV inhibitor of the present invention.For example, clearly contain separately or can conform to ingest through regulating at interval, for example once or once above rule when ingesting (during during for example at breakfast and/or at lunch and/or in dinner time or the like) with individuality with the administration time of the GPR119 agonist of DPP-IV inhibitor combination.Also can use the value of selected GPR119 agonist concentration scope or the value of selected DPP-IV inhibitor concentration scope to determine that administration time is at interval to realize the expection therapeutical effect.Should use the scheme that in the time of 10%-90%, plasma content is maintained respectively in selected GPR119 agonist concentration scope and/or the DPP-IV inhibitor concentration scope to throw and GPR119 agonist and/or DPP-IV inhibitor, be in the time of 30%-99% in specific embodiment, and in embodiment more specifically, be in the time of 50%-90%.Under the situation of topical administration or selectivity absorption, provide and expect that the GPR119 agonist concentration scope and/or the DPP-IV inhibitor concentration scope of therapeutical effect may be not relevant with plasma concentration.

Certainly, the amount with compositions of throwing will depend on the individuality that stands to treat, individual body weight, ailing seriousness, dosing mode and prescriber's judgement.

On the one hand, therefore the present invention provides a kind of treatment or prevention to be characterised in that the condition of illness (for example osteoporosis) of low bone mass or increases the method for bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention, or is made up of a certain amount of GPR119 agonist according to the present invention basically.In certain embodiments, compositions is a medical composition.

On the one hand, therefore the present invention provides a kind of treatment or prevention to be characterised in that the condition of illness (for example osteoporosis) of low bone mass or increases the method for bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor according to the present invention a certain amount of basically.In certain embodiments, compositions is a medical composition.

On the one hand, the present invention relates to the method that a kind of treatment or prevention are characterised in that the condition of illness (for example osteoporosis) of low bone mass or increase bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor according to the present invention a certain amount of basically.In related fields, the invention provides described method, wherein GPR119 agonist and DPP-IV inhibitor are to throw with the amount that is enough to provide treatment or prevention to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and/or to increase the effect of individual bone mass to be characterised in that the condition of illness (for example osteoporosis) of low bone mass with, the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount for treatment or prevention and/or to increase the individual bone mass ineffective in treatment.In certain embodiments, compositions is a medical composition.

On the one hand, the present invention relates to the method that a kind of treatment or prevention are characterised in that the condition of illness (for example osteoporosis) of low bone mass or increase bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor according to the present invention a certain amount of basically.In related fields, the invention provides described method, wherein GPR119 agonist and DPP-IV inhibitor be with the amount that is enough to provide treatment or prevention to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and/or to increase the effect of individual bone mass throw with, wherein said effect is a synergism.In certain embodiments, compositions is a medical composition.

On the one hand, the present invention relates to the method that a kind of treatment or prevention are characterised in that the condition of illness of low bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor according to the present invention a certain amount of basically.In related fields, the invention provides described method, wherein GPR119 agonist and DPP-IV inhibitor be with the amount that is enough to provide treatment or prevention to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and/or to increase the effect of individual bone mass throw with, wherein said effect is a synergism, and the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is characterised in that the condition of illness (for example osteoporosis) of low bone mass for treatment or prevention and/or increases the individual bone mass ineffective in treatment.In certain embodiments, compositions is a medical composition.

On the one hand, the present invention relates to the method that a kind of treatment or prevention are characterised in that the condition of illness of low bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor according to the present invention a certain amount of basically.In related fields, the invention provides described method, wherein GPR119 agonist and DPP-IV inhibitor are to throw and, wherein effect that is provided separately greater than the GPR119 agonist by described amount by the effect that combination provided of the DPP-IV inhibitor of the GPR119 agonist of described amount and described amount and the effect that provided separately by the DPP-IV inhibitor of described amount with the amount that is enough to provide treatment or prevention to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and/or to increase the effect of individual bone mass.In certain embodiments, compositions is a medical composition.

On the one hand, the present invention relates to the method that a kind of treatment or prevention are characterised in that the condition of illness (for example osteoporosis) of low bone mass or increase bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention, or is made up of a certain amount of GPR119 agonist according to the present invention basically.In related fields, the invention provides described method, wherein the GPR119 agonist be with the amount that is enough to provide the effect that increases individual GIP content throw with.In certain embodiments, compositions is a medical composition.

On the one hand, the present invention relates to the method that a kind of treatment or prevention are characterised in that the condition of illness (for example osteoporosis) of low bone mass or increase bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor according to the present invention a certain amount of basically.In related fields, the invention provides described method, wherein GPR119 agonist and DPP-IV inhibitor be with the amount that is enough to provide the effect that increases individual GIP content throw with.In certain embodiments, compositions is a medical composition.

On the one hand, the present invention relates to the method that a kind of treatment or prevention are characterised in that the condition of illness (for example osteoporosis) of low bone mass or increase bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor according to the present invention a certain amount of basically.In related fields, the invention provides described method, wherein GPR119 agonist and DPP-IV inhibitor be with the amount that is enough to provide the effect that increases individual GIP content throw with, and the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is ineffective in treatment for increasing individual GIP content.In certain embodiments, compositions is a medical composition.

On the one hand, the present invention relates to the method that a kind of treatment or prevention are characterised in that the condition of illness (for example osteoporosis) of low bone mass or increase bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor according to the present invention a certain amount of basically.In related fields, the invention provides described method, wherein GPR119 agonist and DPP-IV inhibitor be with the amount that is enough to provide the effect that increases individual GIP content throw with, and wherein said effect is a synergism.In certain embodiments, compositions is a medical composition.

On the one hand, the present invention relates to the method that a kind of treatment or prevention are characterised in that the condition of illness of low bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor according to the present invention a certain amount of basically.In related fields, the invention provides described method, wherein GPR119 agonist and DPP-IV inhibitor be with the amount that is enough to provide the effect that increases individual GIP content throw with, wherein said effect is a synergism, and the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is ineffective in treatment for increasing individual GIP content.In certain embodiments, compositions is a medical composition.

On the one hand, the present invention relates to the method that a kind of treatment or prevention are characterised in that the condition of illness of low bone mass, it comprises to the individuality that needs are arranged throws and the compositions for the treatment of effective dose, described compositions comprises a certain amount of according to GPR119 agonist of the present invention and a certain amount of according to DPP-IV inhibitor of the present invention, or is made up of according to GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor according to the present invention a certain amount of basically.In related fields, the invention provides described method, wherein GPR119 agonist and DPP-IV inhibitor are to throw and, wherein effect that is provided separately greater than the GPR119 agonist by described amount by the effect that combination provided of the DPP-IV inhibitor of the GPR119 agonist of described amount and described amount and the effect that provided separately by the DPP-IV inhibitor of described amount with the amount that is enough to provide the effect that increases individual GIP content.In certain embodiments, compositions is a medical composition.

In certain embodiments, GIP content is the total GIP content of blood or blood plasma.In certain embodiments, GIP content is blood or blood plasma biological activity GIP content.

Therapy of the present invention can be used for increasing individual bone formation.

Therapy of the present invention (promptly with relevant with the GPR119 agonist of DPP-IV inhibitor combination according to circumstances therapy and comprise and above-mentioned GPR119 agonist and the relevant combination treatment of DPP-IV inhibitor) can be used for treating or prevents the individual condition of illness of low bone mass and the bone mass that increases individuality of being characterised in that.

In certain embodiments, the individuality of accepting therapy of the present invention (promptly with relevant with the GPR119 agonist of DPP-IV inhibitor combination according to circumstances therapy and comprise and above-mentioned GPR119 agonist and the relevant combination treatment of DPP-IV inhibitor) is human, and the participant in the research sells the government organs of approval and examines by being responsible for medicine.In certain embodiments, described research is clinical trial.In certain embodiments, described government organs are food and drug administration (Food and Drug Administration of the United States).

The condition of illness that is characterised in that low bone mass includes, but is not limited to osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer to be reduced.In certain embodiments, be characterised in that the condition of illness that hangs down bone mass is osteoporosis.In certain embodiments, be characterised in that the condition of illness that hangs down bone mass is osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.Be characterised in that the condition of illness of low bone mass also includes, but is not limited to the long-term complications of osteoporosis, for example rachiocamposis, height reduce and the restoration operation.Should be appreciated that, be characterised in that the condition of illness of low bone mass can individually or with any combination be included among the embodiment.In certain embodiments, be characterised in that the condition of illness that hangs down bone mass is primary osteoporosis.

In certain embodiments, the bmd (BMD) that need to increase the individuality of bone mass be lower than Young Adults with reference to the amount of meansigma methods greater than 1 (T-scoring＜-1), more than or equal to 1.5 (T-scoring≤-1.5), more than or equal to 2 (T-scoring≤-2) or more than or equal to the individual standard deviation in 2.5 (T-scoring≤-2.5).In certain embodiments, need to increase the individual need treatment fracture of bone mass.In certain embodiments, need the individuality of treatment fracture to have traumatic fracture, fracture or osteoporotic fracture for a long time.In certain embodiments, individual need treatment osteopathia.In certain embodiments, needing the individuality of treatment osteopathia to have osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis or height sick, that cause because of metastatic cancer reduces.In certain embodiments, need the individuality of treatment osteopathia to have osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.The destructive bone disorders that can treat according to the present invention includes, but is not limited to osteoporosis, primary osteoporosis, secondary osteoporosis, osteoarthritis and osteolytic lesion (for example by osteolytic lesion that neoplastic disease, X-ray therapy or chemotherapy caused).

Therapy of the present invention (promptly with relevant with the GPR119 agonist of DPP-IV inhibitor combination according to circumstances therapy and comprise and above-mentioned GPR119 agonist and the relevant combination treatment of DPP-IV inhibitor) can be used for treatment in addition and fractures.In certain embodiments, need the individuality of treatment fracture to have traumatic fracture, fracture or osteoporotic fracture for a long time.

Therapy of the present invention (promptly with relevant with the GPR119 agonist of DPP-IV inhibitor combination according to circumstances therapy and comprise and combination treatment that above-mentioned GPR119 agonist and DPP-IV inhibitor are correlated with) can be used for treating osteopathia in addition.In certain embodiments, needing the individuality of treatment osteopathia to have osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis or height sick, that cause because of metastatic cancer reduces.In certain embodiments, need the individuality of treatment osteopathia to have osteoporosis.In certain embodiments, osteoporosis is a primary osteoporosis.In certain embodiments, osteoporosis is a secondary osteoporosis.The destructive bone disorders that can treat according to the present invention includes, but is not limited to osteoporosis, primary osteoporosis, secondary osteoporosis, osteoarthritis and osteolytic lesion (for example by osteolytic lesion that neoplastic disease, X-ray therapy or chemotherapy caused).

Therapy of the present invention (promptly with relevant with the GPR119 agonist of DPP-IV inhibitor combination according to circumstances therapy and comprise and above-mentioned GPR119 agonist and the relevant combination treatment of DPP-IV inhibitor) is used in the knitting that strengthens in the individuality after facial reconstructions, upper jaw bone reconstructions, mandibular bone reconstruction, periodontal disease or the exodontia in addition, strengthen long bone extends, strengthens that restoration is inside grows or the increase synosteosis.

In certain embodiments, individuality is a vertebrates.In certain embodiments, be Fish, amphibian, reptile class, birds or mammal as vertebrate individuality.In certain embodiments, individuality or vertebrates are mammals.In certain embodiments, be mice, rat, hamster, rabbit, pig, Canis familiaris L., cat, horse, cattle, sheep, goat, non-human mammal, non-human primate or the mankind as mammiferous individuality or vertebrates.In certain embodiments, individuality is human.In certain embodiments, the mankind are postmenopausal womens or surpass 50 years old male.

Test kit

The present invention also is provided for implementing the test kit of aforesaid calibration method.

In certain embodiments, test kit comprises compositions that comprises the GPR119 agonist and the description of implementing calibration method (for example, treatment or prevention are characterised in that the method for the condition of illness (for example osteoporosis) of low bone mass, the method for the individual bone mass of increase etc.) about the component of using test kit at least.In certain embodiments, the GPR119 agonist is dosage form.In certain embodiments, compositions is a medical composition.

In certain embodiments, test kit comprises compositions that comprises the GPR119 agonist and the compositions that comprises the DPP-IV inhibitor at least and implements the description of calibration method (for example, treatment or prevention are characterised in that the method for the condition of illness (for example osteoporosis) of low bone mass, the method for the individual bone mass of increase etc.) about the component of using test kit.In certain embodiments, GPR119 agonist and/or DPP-IV inhibitor are dosage form.In certain embodiments, the compositions that comprises the compositions of GPR119 agonist and comprise the DPP-IV inhibitor is a medical composition.

In certain embodiments, test kit comprises the compositions of the combination that comprises GPR119 agonist and DPP-IV inhibitor at least and implements the description of calibration method (for example, treatment or prevention are characterised in that the method for the condition of illness (for example osteoporosis) of low bone mass, the method for the individual bone mass of increase etc.) about the component of using test kit.In certain embodiments, the combination of GPR119 agonist and DPP-IV inhibitor is dosage form.In certain embodiments, compositions is a medical composition.

Clearly contain description and can comprise at least that (with the form of description alone or in combination) implement the dosage information of calibration method and in the educational information one or both about the component of using test kit.Educational material can relate to calibration method than security implementation, implement the higher compliance of calibration method etc.Usually be recorded on the suitable recording medium about the description of implementing calibration method.For instance, description for example can be printed on the substrate such as paper or plastics.Equally, description can the package insert form be present in the test kit, be present in (promptly combining with packing or inner packing) etc. in the containers labels of test kit or its component.In other embodiments, description is to exist with the form that is present in the electronics storing data files on the suitable computer-readable recording medium (for example CD-ROM, disk etc.).In other embodiments, the practical illustration book is not present in the test kit, but the mode that is obtained description by remote source (for example passing through the Internet) is provided.The example of this embodiment is to comprise the test kit that can browse description and/or can download the network address of description.As description, the mode of this acquisition description also is recorded in and is fit on the substrate.

Need not to be described in further detail, believe that the those skilled in the art can use previous description farthest to implement the present invention.Preamble only describe in detail for clear understand provide, and should not be construed as its unnecessary restriction obviously recognize within the scope of the present invention change because the those skilled in the art can become.

The application's case advocate shown in the date by U.S.'s express mail (U.S.Express mail) priority to the following provisional application case of United States Patent and Trademark Office (United States Patent and Trademark Office) application: No. the 60/791st, 613, the U.S. Provisional Application case of application on April 11st, 2006; No. the 60/834th, 737, the U.S. Provisional Application case of application on July 31st, 2006; With No. the 60/851st, 244, the U.S. Provisional Application case of on October 12nd, 2006 application; Being incorporated herein by reference in full of its disclosure separately.

The application's case in the whole text in, quote various open case, patent and patent application cases.The disclosure of the open case of these that in the application's case, mention, patent and patent application case be to incorporate among the present invention by reference in full.The applicant is not that the applicant admits that described open case, patent or patent application case are background technologies to quoting of open case, patent or patent application case in this article.

Example

Need not to be described in further detail, believe that the those skilled in the art can use previous description farthest to implement the present invention.It is illustrative that following detailed example only should be understood that, and be not to limit aforementioned disclosure by any way.The those skilled in the art will recognize the appropriate change of program rapidly.

Example 1: throw and the pharmacodynamic analysis of GPR119 agonist to the influence of wild-type mice blood GIP content

A. make C57blk/6 male mice fasting 18 hours, and be randomly assigned in 14 groups, the n=6 of each group.With mediator (PET; 80% PEG400,10% ethanol, 10% Tween80) or with 20 milligrams/kilogram according to GPR119 agonist (chemical compound 1Z of the present invention; (2-fluoro-4-methane sulfonyl-phenyl)-6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidines-1-yl]-5-nitro-pyrimidine-4-yl }-amine) mice is carried out oral administration (as shown in Figure 1A).In treatment in the time of back 30 minutes, per os transmits the glucose bolus of 3 gram/kilograms, and behind the glucose bolus collection blood plasma when 0 minute (no glucose bolus), 2 minutes, 5 minutes, 10 minutes, 20 minutes, 40 minutes and 60 minutes.By using rodent GIP ELISA test kit [rat/mouse CIP (always) ELISA available from Lin Ke research laboratory (Linco Research Laboratory), catalog number (Cat.No.) EZRMGIP-55K], measure blood plasma GIP content according to the description that supplier provided.According to the result shown in Figure 1A, apparent throwing and GPR119 agonist increase glucose dependency and the glucose dependent/non-dependent GIP content in the mouse blood simultaneously.Chemical compound 1Z stimulates the total GIP of blood plasma of mice.The chemical compound that is disclosed in chemical compound 1Z and the international application PCT/US2004/001267 number (open with WO 2004/065380) is identical.

B. make C57blk/6 male mice fasting 18 hours, and be randomly assigned in 14 groups, the n=6 of each group.With mediator (20% hydroxypropyl-beta-schardinger dextrin-(HPCD)) or with 10 milligrams/kilogram according to GPR119 agonist of the present invention (chemical compound 3Z) mice is carried out oral administration (as shown in Figure 1B).In treatment in the time of back 30 minutes, per os transmits the glucose bolus of 3 gram/kilograms, and behind the glucose bolus collection blood plasma when 0 minute (no glucose bolus), 5 minutes, 10 minutes, 20 minutes, 60 minutes and 120 minutes.By using rodent GIP ELISA test kit [rat/mouse CIP (always) ELISA available from Lin Ke research laboratory (Linco Research Laboratory), catalog number (Cat.No.) EZRMGIP-55K], measure blood plasma GIP content according to the description that supplier provided.Use the Excel program to carry out statistical analysis.Calculate the meansigma methods of GIP concentration and represent according to the result of six mices in each group with meansigma methods ± SEM.According to the result shown in Figure 1B, apparent throwing and GPR119 agonist increase glucose dependency and the glucose dependent/non-dependent GIP content in the mouse blood simultaneously.Chemical compound 3Z stimulates the total GIP of blood plasma of mice.The chemical compound that is disclosed in chemical compound 3Z and the international application PCT/US2004/022327 number (open with WO 2005/007647) is identical.

C. make C57blk/6 male mice fasting 18 hours, and be randomly assigned in 14 groups, the n=6 of each group.With mediator (20% hydroxypropyl-beta-schardinger dextrin-(HPCD)) or according to GPR119 agonist of the present invention (chemical compound 3Z) mice is carried out oral administration with 1 milligram/kilogram, 3 milligrams/kilogram or 10 milligrams/kilogram.In treatment in the time of back 30 minutes, per os transmits the glucose bolus of 3 gram/kilograms, and behind the glucose bolus collection blood plasma when 0 minute (no glucose bolus) or 5 minutes.By using rodent GIP ELISA test kit [rat/mouse CIP (always) ELISA available from Lin Ke research laboratory (Linco Research Laboratory), catalog number (Cat.No.) EZRMGIP-55K], measure blood plasma GIP content according to the description that supplier provided.Use the Excel program to carry out statistical analysis.Calculate the meansigma methods of GIP concentration and be shown among Fig. 1 C according to the result of six mices in each group.According to Fig. 1 C, apparent GPR119 agonist (chemical compound 3Z) stimulates the total GIP of blood plasma of mice in the dose dependent mode.The chemical compound that is disclosed in chemical compound 3Z and the international application PCT/US2004/022327 number (open with WO 2005/007647) is identical.

Example 2: throwing and GPR119 agonist are to the influence of GPR119 deletion form (rejecting) mice compared to the blood GIP content of wild-type mice

A. make GPR119 deletion form male mice and the fasting of wild type littermate 18 hours.With mediator (PET; 80% PEG400,10% ethanol, 10% Tween80) or with 20 milligrams/kilogram according to GPR119 agonist (chemical compound 1Z of the present invention; (2-fluoro-4-methane sulfonyl-phenyl)-6-[4-(the 3-isopropyl-[1,2,4] oxadiazole-5-yls)-piperidines-1-yl]-5-nitro-pyrimidine-4-yl }-amine) mice is carried out oral administration ((n=5) as shown).In the time of back 30 minutes, gather blood (100 microlitre) (time 0) in treatment, then throw glucose bolus (per os) with 3 gram/kilograms by the eye socket posterior vein of eye.After transmitting glucose, 5 minutes the time, gather another blood sample (100 microlitre) (5 minutes time).Collect blood plasma and pass through rodent GIP ELISA test kit [rat/mouse CIP (always) ELISA of use in centrifugal back available from Lin Ke research laboratory (Linco Research Laboratory), catalog number (Cat.No.) EZRMGIP-55K], measure GIP content according to the description that supplier provided.According to the result shown in Fig. 2 A, apparent functional GPR119 receptor for throw and GPR119 agonist the glucose dependent/non-dependent GIP content and the glucose dependency GIP content that increase in the mouse blood be essential.Chemical compound 1Z stimulates the total GIP of blood plasma of wild-type mice.The chemical compound that is disclosed in chemical compound 1Z and the international application PCT/US2004/001267 number (open with WO 2004/065380) is identical.

B. make GPR119 deletion form male mice and the fasting of wild type littermate 18 hours.With mediator (40% hydroxypropyl-beta-schardinger dextrin-(HPCD)) or with 30 milligrams/kilogram according to GPR119 agonist of the present invention (chemical compound 2Z) mice is carried out oral administration ((n=5) as shown).In the time of back 30 minutes, gather blood (100 microlitre) (time 0) in treatment, then throw glucose bolus (per os) with 3 gram/kilograms by the eye socket posterior vein of eye.After transmitting glucose, 5 minutes the time, gather another blood sample (100 microlitre) (5 minutes time).Collect blood plasma and pass through rodent GIP ELISA test kit [rat/mouse CIP (always) ELISA of use in centrifugal back available from Lin Ke research laboratory (Linco Research Laboratory), catalog number (Cat.No.) EZRMGIP-55K], measure GIP content according to the description that supplier provided.Calculate the meansigma methods of GIP concentration according to the result of five mices in each group.According to the result shown in Fig. 2 B, apparent functional GPR119 receptor for throw and GPR119 agonist the glucose dependent/non-dependent GIP content and the glucose dependency GIP content that increase in the mouse blood be essential.Chemical compound 2Z stimulates the total GIP of blood plasma of wild-type mice.The chemical compound that is disclosed in chemical compound 2Z and the international application PCT/US2004/022417 number (open with WO2005/007658) is identical.

Example 3: the combination of throwing and GPR119 agonist and DPP-IV inhibitor is to the influence of the blood GIP content of wild-type mice

Use in vivo analysis hereinafter described, can show according to the GIP content in the combination increase individual blood of a certain amount of GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor.

Make C57blk/6 male mice fasting 18 hours, and be randomly assigned in 14 groups, the n=6 of each group.With mediator (PET; 80% PEG400,10% ethanol, 10% Tween80) or the combination of a certain amount of GPR119 agonist and a certain amount of DPP-IV inhibitor mice is carried out oral administration.The experimental group of experimental group and above-mentioned example 1 is similar.The GPR119 agonist of combination and each in the DPP-IV inhibitor are to use with the amount between 0.001 milligram/kg body weight and 100 milligrams/kg body weight.In treatment in the time of back 30 minutes, per os transmits the glucose bolus of 3 gram/kilograms, and behind the glucose bolus collection blood plasma when 0 minute (no glucose bolus), 2 minutes, 5 minutes, 10 minutes, 20 minutes, 40 minutes and 60 minutes.By using rodent GIP ELISA test kit [rat/mouse CIP (always) ELISA available from Lin Ke research laboratory (Linco ResearchLaboratory), catalog number (Cat.No.) EZRMGIP-55K], measure blood plasma GIP content according to the description that supplier provided.

In relevant programme, analysis can comprise mice warp the additional experiments group and/or the independent additional experiments group of injecting the DPP-IV inhibitor of described amount of mice warp of the GPR119 agonist of the described amount of injection separately.

Use aforementioned in vivo analysis, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide the amount of the effect of increase individual blood GIP content to provide, the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is ineffective in treatment for increasing individual blood GIP content.

Use aforementioned in vivo analysis, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide the amount of the effect of increase individual blood GIP content to provide, wherein said effect is a synergism.

Use aforementioned in vivo analysis, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide the amount of the effect of increase individual blood GIP content to provide, wherein said effect is a synergism, and the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is ineffective in treatment for increasing individual blood GIP content.

Use aforementioned in vivo analysis, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide to increase the amount of the effect of individual blood GIP content to provide, wherein effect that provides separately greater than GPR119 agonist by the effect that combination provided of GPR119 agonist and DPP-IV inhibitor and the effect that provides separately by the DPP-IV inhibitor of described amount by described amount.

Example 4: the combination of throwing and GPR119 agonist and DPP-IV inhibitor is to the pharmacodynamic analysis of the influence of wild-type mice blood GIP content

Use the above in vivo analysis of example 3, show according to the GIP content in the combination increase individual blood of a certain amount of GPR119 agonist of the present invention and a certain amount of DPP-IV inhibitor.

Make C57blk/6 male mice fasting 18 hours, and be randomly assigned in 24 groups, the n=6 of each group.With mediator (PET; 80% PEG400,10% ethanol, 10% Tween80), with independent 1 milligram/kilogram according to DPP-IV inhibitor of the present invention (AR247810) or use according to GPR119 agonist of the present invention 10 milligrams/kilogram ((2-fluoro-4-methane sulfonyl-phenyl)-{ 6-[4-(3-isopropyl-[1; 2,4] oxadiazole-5-yl)-piperidines-1-yl]-5-nitro-pyrimidine-4-yl }-amine) with the combination of 1 milligram/kilogram DPP-IV inhibitor (AR247810) mice is carried out oral administration (as shown in Figure 3).In treatment in the time of back 30 minutes, per os transmits the glucose bolus of 3 gram/kilograms, and behind the glucose bolus collection blood plasma when 0 minute (no glucose bolus), 5 minutes, 10 minutes, 20 minutes, 40 minutes, 60 minutes, 90 minutes and 120 minutes.By using rodent GIP ELISA test kit [rat/mouse CIP (always) ELISA available from Lin Ke research laboratory (Linco Research Laboratory), catalog number (Cat.No.) EZRMGIP-55K], measure the total GIP content of blood plasma according to the description that supplier provided.

According to the result shown in Fig. 3, the combination of the GPR119 agonist of apparent throwing and amount according to the present invention and the DPP-IV inhibitor of described amount as one man provides the effect that increases GIP content in the mouse blood, and it is greater than the independent effect that provides of DPP-IV inhibitor by described amount.

Example 5: throw and of the influence of GPR119 agonist to the bone mass of ovariectomized rat

Use in vivo oophorectomize (OVX) rat model hereinafter described is [for example referring to Bo Lage people such as (Bollag), molecular cell endocrinology (Mol Cell Endocrinol) (2001) 177:35-41], show according to GPR119 agonist of the present invention and can effectively treat or prevent to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and/or increase individual bone mass.

From Ha Lansi Prey Ge-(Harlan Sprague-Dawley of Dao Li company, Inc.) (20 the not female OVX of copulation and 20 the non-OVX Si Puleige-Dao Li of copulation (Sprague-Dawley) rats (150 grams-175 grams) (8 age in week) are not buied in Bo Lisi city, Indiana, USA Indiana (Indianapolis, IN)).Make the arbitrarily edible common commercially available rounded grain feedstuff Tyke of animal draw (Teklab) rodent (1.46% calcium), and it is freely drunk water.Rat is divided into the experimental group that four weight match at random and selected and accept mediator or according to GPR119 agonist of the present invention with per os.Treat every day, continued for 6 weeks.

1. matched group.10 non-OVX rat orals are thrown and mediator.

2. matched group+treatment.10 non-OVX rat orals are thrown and the GPR119 agonist.

3.OVX。10 OVX rat orals are thrown and mediator.

4.OVX+ treatment.10 OVX rat orals are thrown and the GPR119 agonist.

Every day rat is weighed and measuring body is long once more in baseline and the 6th when week.Before the treatment beginning and when the 6th week, make and make good use of happy outstanding (Hologic) QDR 1000/W (Massachusetts Wo Shamu city (Waltham, MA)) all animals are carried out dual-energy x-ray absorption process (DXA), and use 5.53 editions analytical data of software rat body (Rat Whole Body).Measure bmd (BMD) at the spinal column place.

Measure the variation percentage ratio for the treatment of the back spine density 6 weeks.Show to throw and weaken the negative effect of ovariectomy spine density with the GPR119 agonist.Ovariectomy shows that to the weakening of the negative effect of spine density described treatment has treatment or prevention is characterised in that condition of illness (for example osteoporosis) that hangs down bone mass and/or the effect that increases individual bone mass.

Example 6: the combination of throwing and GPR119 agonist and DPP-IV inhibitor is to the influence of the bone mass of ovariectomized rat

Use in vivo oophorectomize (OVX) rat model hereinafter described is [for example referring to Bo Lage people such as (Bollag), molecular cell endocrinology (Mol Cell Endocrinol) (2001) 177:35-41], show according to the combination of GPR119 agonist of the present invention and DPP-IV inhibitor and can effectively treat or prevent to be characterised in that the condition of illness (for example osteoporosis) of low bone mass and/or increase individual bone mass.

From Ha Lansi Prey Ge-(Harlan Sprague-Dawley of Dao Li company, Inc.) (20 the not female OVX of copulation and 20 the non-OVX Si Puleige-Dao Li of copulation (Sprague-Dawley) rats (150 grams-175 grams) (8 age in week) are not buied in Bo Lisi city, Indiana, USA Indiana (Indianapolis, IN)).Make the arbitrarily edible common commercially available rounded grain feedstuff Tyke of animal draw (Teklab) rodent (1.46% calcium), and it is freely drunk water.Rat is divided into the experimental group that four weight match at random and selected and accept mediator or according to the combination of GPR119 agonist of the present invention and DPP-IV inhibitor with per os.Treat every day, continued for 6 weeks.

1. matched group.10 non-OVX rat orals are thrown and mediator.

2. matched group+treatment.10 non-OVX rat orals are thrown the combination with GPR119 agonist and DPP-IV inhibitor.

3.OVX。10 OVX rat orals are thrown and mediator.

4.OVX+ treatment.10 OVX rat orals are thrown the combination with GPR119 agonist and DPP-IV inhibitor.

Every day rat is weighed and measuring body is long once more in baseline and the 6th when week.Before the treatment beginning and when the 6th week, make and make good use of happy outstanding (Hologic) QDR1000/W (Massachusetts Wo Shamu city (Waltham, MA)) all animals are carried out dual-energy x-ray absorption process (DXA), and use 5.53 editions analytical data of software rat body (Rat Whole Body).

Use above-mentioned in vivo analysis, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide the weakening ovariectomy that the amount of the effect of the negative effect of spine density is provided, the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is ineffective in treatment concerning the negative effect of spine density for weakening ovariectomy.

Use above-mentioned in vivo analysis, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide the weakening ovariectomy that the amount of the effect of the negative effect of spine density is provided, wherein said effect is a synergism.

Use above-mentioned in vivo analysis, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide the weakening ovariectomy that the amount of the effect of the negative effect of spine density is provided, wherein said effect is a synergism, and the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is ineffective in treatment concerning the negative effect of spine density for weakening ovariectomy.

Use above-mentioned in vivo analysis, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide to weaken ovariectomy that the amount of the effect of the negative effect of spine density is provided, wherein effect that provides separately greater than GPR119 agonist by the effect that combination provided of GPR119 agonist and DPP-IV inhibitor and the effect that provides separately by the DPP-IV inhibitor of described amount by described amount.

Example 7: throw and of the influence of GPR119 agonist to union of fracture

Use in vivo analysis hereinafter described, show and effectively to treat fracture according to GPR119 agonist of the present invention.

The fracture technology

With ketamine (Ketamine) Si Puleige-Dao Li (Sprague-Dawley) rat at 3 monthly ages of anesthesia.On the anteromedial surface of right tibia or Thigh bone proximal part, make 1 centimetre otch.The tibia surgical technic is hereinafter described.With described incision extension to bone, and nearside apart from 4 millimeters of described tibial tubercle far-ends and central authorities get out 1 millimeter hole apart from 2 millimeters places of leading edge.With 0.8 millimeter stainless steel tube carry out intramedullary pin fix (peak load 36.3 newton, highest hardness 61.8 Newton/millimeter, with bone photo with condition under test).Do not carry out the reaming of spinal canal.By the adjustable tweezers that use particular design with blunt pawl carry out three-point bending and above tibiofibular joint 2 millimeters places cause the closed fracture of standard.Minimum for soft tissue injury is dropped to, note not making displacement fracture.Use the monofilament nylon suture skin suture.Described operation is carried out under aseptic condition.Immediately all fracture are carried out radiography after fixing following closely, and get rid of the rat that outside specifying backbone area, has fracture or have the displacement nail.To remain animal and be divided into following group (each group of each time point has 10-12 animal) at random with the test union of fracture.Every day is to described rat oral throwing and mediator or GPR119 agonist.The GPR119 agonist is to use between the amount between 100 milligrams of 0.001 milligram of per kilogram of body weight and the pers kilogram of body weight.Continued treatment 10 days, 20 days, 40 days and 80 days.

When the 10th day, the 20th day, the 40th day and the 80th day, make its death with 10-12 rat of each group of Patients Under Ketamine Anesthesia and by blood-letting.Shift out two tibiofibulas and peel off all soft tissues by dissection.The bone of 5-6 rat of each group is stored in 70% ethanol to carry out histologic analysis, and the bone of other 5-6 rat of each group is stored in the buffering Ringer's mixture (Ringer ' s solution) (+4 ℃, pH 7.4) to carry out the test of radiography and bio-mechanical.

Histologic analysis

The histologic analysis method of fracture property bone was before announced by Mo Sekede (Mosekilde) and Bark (Bak) [bone (Bone) (1993) 14:19-27].In brief, fracture site is cut 8 millimeters places of each side of astragalus broken line, be embedded in the methyl methacrylate, and cut out the front section of 8 micron thickness with the many cut types of Lei Chete-Jung (Reichert-Jung Polycut) microtome in not decalcification mode.Use in Ma Sen-trichroism (Masson-Trichome) is painted-just cut into slices (comprising tibia and fibula) carry out for having or not the cell of union of fracture and the developing of tissue reaction under the treatment situation.The feature of use shark bone crust structure through the painted section of Sirius red (Sirius red) is also distinguished woven bone and the fracture site of stratiform bone.Carry out following measurement: (1) fracture gap-measure with the beeline between the cortical bone end in the fracture, (2) callus length and callus diameter, (3) total bone volume zone of callus, (4) the sclerotin tissue of each tissue regions of callus intra-zone, the cartilage zone in the fibrous tissue in (5) callus and (6) callus.

Bio-mechanical is analyzed

The method that bio-mechanical is analyzed was before announced by Bark (Bak) and Anderson (Andreassen) [(1989) 45:292-297 of international calcified tissue (Calcif Tissue Int)].In brief, before the bio-mechanical test, all fracture are carried out radiography.Analyze the mechanical property of healing fracture by 3 of destructivenesses or four-point bending program.Measure peak load, hardness, the energy of busy hour, the deflection and the maximum stress of busy hour.

Example 8: the combination of throwing and GPR119 agonist and DPP-IV inhibitor is to the influence of union of fracture

Use in vivo analysis hereinafter described, show and effectively to treat fracture according to the combination of GPR119 agonist of the present invention and DPP-IV inhibitor.

Use in vivo analysis hereinafter described, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide the amount of the effect of the individual fracture of treatment to provide, the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is ineffective in treatment for the individual fracture of treatment.

Use in vivo analysis hereinafter described, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide the amount of the effect of the individual fracture of treatment to provide, wherein said effect is a synergism.

Use in vivo analysis hereinafter described, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide the amount of the effect of the individual fracture of treatment to provide, wherein said effect is a synergism, and the independent DPP-IV inhibitor of the independent GPR119 agonist of wherein said amount and described amount is ineffective in treatment for the individual fracture of treatment.

Use in vivo analysis hereinafter described, can show that GPR119 agonist and DPP-IV inhibitor can be enough to make combination to provide the amount of the effect of the individual fracture of treatment to provide, wherein effect that provides separately greater than GPR119 agonist by the effect that combination provided of GPR119 agonist and DPP-IV inhibitor and the effect that provides separately by the DPP-IV inhibitor of described amount by described amount.

The fracture technology

With ketamine (Ketamine) Si Puleige-Dao Li (Sprague-Dawley) rat at 3 monthly ages of anesthesia.On the anteromedial surface of right tibia or Thigh bone proximal part, make 1 centimetre otch.The tibia surgical technic is hereinafter described.With described incision extension to bone, and nearside apart from 4 millimeters of described tibial tubercle far-ends and central authorities get out 1 millimeter hole apart from 2 millimeters places of leading edge.With 0.8 millimeter stainless steel tube carry out intramedullary pin fix (peak load 36.3 newton, highest hardness 61.8 Newton/millimeter, with bone photo with condition under test).Do not carry out the reaming of spinal canal.By the adjustable tweezers that use particular design with blunt pawl carry out three-point bending and above tibiofibular joint 2 millimeters places cause the closed fracture of standard.Minimum for soft tissue injury is dropped to, note not making displacement fracture.Use the monofilament nylon suture skin suture.Described operation is carried out under aseptic condition.Immediately all fracture are carried out radiography after fixing following closely, and get rid of the rat that outside specifying backbone area, has fracture or have the displacement nail.To remain animal and be divided into following group (each group of each time point has 10-12 animal) at random with the test union of fracture.Every day is to the combination of described rat oral throwing and mediator or GPR119 agonist and DPP-IV inhibitor.Each combination of GPR119 agonist and DPP-IV inhibitor is with between the amount use between 100 milligrams of 0.001 milligram of per kilogram of body weight and the pers kilogram of body weight.After 30 minutes, per os transmits the glucose bolus of 3 gram/kilograms.Continued treatment 10 days, 20 days, 40 days and 80 days.

When the 10th day, the 20th day, the 40th day and the 80th day, make its death with 10-12 rat of each group of Patients Under Ketamine Anesthesia and by blood-letting.Shift out two tibiofibulas and peel off all soft tissues by dissection.The bone of 5-6 rat of each group is stored in 70% ethanol carrying out histologic analysis, and the bone of other 5-6 rat of each group is stored in the buffering Ringer's mixture (+4 ℃, pH 7.4) to carry out the test of radiography and bio-mechanical.

Histologic analysis

Bio-mechanical is analyzed

The melanocyte analysis of example 9:GPR119 agonist activity

Such as Bo Tancha people's [pigment cell studies (Pigment Cell Research) (1992) 5:372-378] such as (Potenza) report remain on melanocyte in the cultivation conditions and use electroporation with coding GPR119 receptor (for example human GPR119,

Deposit numbering AAP72125 and its allele) expression vector carry out transfection.After carrying out electroporation, will be applied in 96 orifice plates to analyze through transfectional cell.Make described cell growth 48 hours subsequently, from the electroporation program, to recover and to obtain maximum expression of receptor amount.

Analyzing the same day, with the growth medium on the buffer displacement cell that does not contain serum that contains the 10nM melatonin.Melatonin is done in order to reduce cAMP content in the cell by the endogenous Gi coupling GPCR in the melanocyte.For responding the reduction of cAMP content, melanocyte is transferred to cell centre with its pigment.The net effect of this situation is that the absorptance reading of cell monolayer in the hole of measuring under 600nM-650nM significantly reduces.

Cultivate after 1 hour in melatonin, cell becomes complete pigment accumulation type.Collect baseline absorptance reading this moment.Serial dilution thing with test compounds adds in the entering plate subsequently, and the chemical compound with GPR119 agonist activity causes the increase of cAMP content in the cell.For responding the cAMP content of these increases, melanocyte shifts its pigment and gets back to cell peripheral.After 1 hour, become complete pigment decentralized through irritation cell.The cell monolayer that is dispersity absorbs more light in the 600nm-650nm scope.Compare measured absorptance increases the quantitative receptor for stimulating degree of permission and draws out dose-effect curve with the baseline reading.

Material and method about the melanocyte analysis see United States Patent (USP) the 5th, 462, and No. 856 and the 6th, 051, in No. 386, being incorporated herein by reference in full of described file disclosure separately.

The active in vitro analysis that suppresses of example 10:DPP-IV

Can use the described in vitro fluorescence analysis assessment of (for example) thunderclap people (journal of biological chemistry (Biochem J) (2003) 371:525-532) such as (Leiting) chemical compound to the active inhibition of DPP-IV.In this analyzes, be to DPP-IV successive analysis 30 minutes among 100mM4-hydroxyethyl piperazine ethanesulfonic acid (Hepes) buffer (pH 7.5) of 100 microlitres and the 0.1 mg/ml BSA at cumulative volume under 37 ℃, and use Spike Thomas Coase Jimmy Buddhist nun (SpectramaxGemini) plate reader (molecular device company (Molecular Devices), Sen Niweier city, California (Sunnyvale, CA)) carries out reading.(wherein AMC represents 7-amino-4-methylcoumarin to use fluorescence peptide Gly-Pro-AMC; Available from Bark nurse company (Bachem), California Torrance (Torrance, CA)) is as the DPP-IV substrate.At the 50 μ M Gly-Pro-AMC (K of Gly-Pro-AMC concentration _mThe IC of the chemical compound that acquisition stands to assess value) ₅₀Value.

Can measure the protease inhibiting activity of DPP-IV inhibitor easily by the known method of those skilled in the art because become known for measuring proteinase activity and test compounds to its inhibition be fit in vitro analyze.

In other the exemplary in vitro analysis that suppresses about DPP-IV, the test compounds solution of the various concentration of preparation (≤10mM ultimate density) in dimethyl sulfoxine (DMSO), and with the analysis buffer that comprises 20mM Tris (pH 7.4), 20mM KCl and 0.1mg/mL BSA it is diluted subsequently.With also cultivating in advance at ambient temperature 10 minutes in human DPP-IV (0.1nM ultimate density) the adding dilution, use A-P-7-amide groups-4-trifluoromethyl coumarin (AP-AFC subsequently; 10 μ M ultimate densities) initial action.Decide on used assay format (384 holes or 96 orifice plates), the cumulative volume of reactant mixture is 10 microlitres-100 microlitres.The kinetics tracking is carried out in reaction (excited λ=400 nanometers; Emission λ=505 nanometers) reach 5-10 minute or after 10 minutes, measure terminal point.Use standard mathematical model calculates inhibition constant (IC according to enzyme process curve ₅₀).

Also can pay and assess chemical compound to the active inhibition of DPP-IV by the company that described service is provided.For instance, can pass through Mei Disheng medical service company (MDS Pharma Services) (catalog number (Cat.No.) 163910; Pu Lushiwang city, Pennsyivania (King of Prussia, PA)) obtain these chemical compounds in the in vitro analysis of using recombinant human DPP-IV about the inhibiting IC of DPP-IV ₅₀Value.

DPP-IV can be human DPP-IV.DPP-IV can be recombinant human DPP-IV.

The full cell adenyl cyclase of example 11:GPR119 agonist activity is analyzed

Ring-type AMP measurement is to use Flash board ^TM(Flash Plate ^TM) adenylate cyclase enzyme reagent kit (New England Niu Kelie company (New England Nuclear)) carries out according to supplier's scheme.With every dish 12 * 10 ⁶The density of individual cell is applied to the HEK293 cell in the conventional growth medium (DMEM/10% FBS) in the 15 cm of tissue culture dishs.Second day, scheme lipofection amine (lipofectamine) (U.S. hero company (Invitrogen) according to manufacturer, Carlsbad, California city (Carlsbad, CA)) is transfected into 10 microgram empty carrier DNA or expression plastid DNA in the cell.Cultivate after 24 hours; to collect in the GIBCO cell dissociation buffer (catalog number (Cat.No.) 13151-014) through transfectional cell; by with 1; centrifugal 5 minutes granulations of 100rpm; and carefully with its resuspending in the analysis buffer of proper volume (50% 1 * PBS and 50% stimulates buffer), obtain 2 * 10 ⁶The final cell counting of individual cells/ml.The test compounds of required analytical concentration shown in the preparation in 50 microlitre analysis buffer, and it is pipetted in the hole of 96 hole Flash boards (Flash Plate).Add above prepared cell suspending liquid (every hole 50 microlitres) subsequently.After at room temperature cultivating time of 60 minutes, subsequently 100 microlitres are contained tracer [ ¹²⁵I]-the detection mixture of cAMP adds in the hand-hole.Plate was cultivated 2 hours again, then counted with Wa Laisi sieve Mike beta (Wallac MicroBeta) scintillation counter.According to the extrapolate value in cAMP/ hole of standard cAMP curve included on each analysis plates.

The increase of cAMP content shows that greater than the increase of cAMP content in the HEK293 of empty carrier transfection cell test compounds is the chemical compound that stimulates the GPR119 function of receptors in the HEK293 of GPR119 transfection cell.

Although aforementioned specification teaching principle of the present invention (example wherein is provided for purposes of illustration) should be appreciated that enforcement of the present invention is encompassed in interior all common variations, rewriting or the change of scope of following claim and its equivalent.

Claims

1. treatment or prevention are characterised in that the method for the condition of illness of low bone mass, and it comprises to the individuality that needs are arranged throws and the GPR119 agonist for the treatment of effective dose.

2. treatment or prevention are characterised in that the method for the condition of illness of low bone mass, and it comprises to the individuality that needs are arranged throws and the medical composition for the treatment of effective dose, and described medical composition comprises GPR119 agonist and pharmaceutically acceptable supporting agent.

3. method according to claim 1 and 2, the wherein said condition of illness that is characterised in that low bone mass are selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man sick (Paget ' s disease), the bone forfeiture, osteolytic lesion, rachiocamposis and the height that cause because of metastatic cancer and reduce the group that forms.

4. method according to claim 1 and 2 wherein saidly is characterised in that the condition of illness of low bone mass is osteoporosis.

5. method that increases bone mass, it comprises to the individuality that needs are arranged throws GPR119 agonist with the treatment effective dose.

6. method that increases bone mass, it comprises to the individuality that needs are arranged throws medical composition with the treatment effective dose, and described medical composition comprises GPR119 agonist and pharmaceutically acceptable supporting agent.

7. according to claim 5 or 6 described methods, the bmd of wherein said individuality (BMD) be lower than Young Adults with reference to the amount of meansigma methods greater than 1 standard deviation (T-scoring＜-1).

8. method for the treatment of fracture, it comprises to the individuality that needs are arranged throws GPR119 agonist with the treatment effective dose.

9. method for the treatment of fracture, it comprises to the individuality that needs are arranged throws medical composition with the treatment effective dose, and described medical composition comprises GPR119 agonist and pharmaceutically acceptable supporting agent.

10. according to Claim 8 or 9 described methods, wherein said individuality has traumatic fracture, fracture or osteoporotic fracture for a long time.

11. a method for the treatment of osteopathia, it comprises to the individuality that needs are arranged throws and the GPR119 agonist for the treatment of effective dose.

12. a method for the treatment of osteopathia, it comprises to the individuality that needs are arranged throws and the medical composition for the treatment of effective dose, and described medical composition comprises GPR119 agonist and pharmaceutically acceptable supporting agent.

13. according to claim 11 or 12 described methods, wherein said osteopathia is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.

14. according to claim 11 or 12 described methods, wherein said osteopathia is an osteoporosis.

15. one kind strengthens knitting after facial reconstructions, upper jaw bone reconstructions, mandibular bone reconstruction, periodontal disease or the exodontia, strengthens long bone and extend, strengthen restoration and inwardly grow or increase synestotic method, it comprises to the individuality throwing that needs are arranged and treats the GPR119 agonist of effective dose.

16. one kind strengthen knitting after facial reconstructions, upper jaw bone reconstructions, mandibular bone reconstruction, periodontal disease or the exodontia, strengthen the long bone extension, the enhancing restoration is inwardly grown or increase synestotic method, it comprises to the individuality that needs are arranged throws and the medical composition for the treatment of effective dose, and described medical composition comprises GPR119 agonist and pharmaceutically acceptable supporting agent.

17. according to the described method of arbitrary claim in the claim 1 to 16, wherein said GPR119 agonist be with the amount of the GIP content that is enough to increase described individuality throw with.

18. according to the described method of arbitrary claim in the claim 1 to 17, wherein said individuality is human.

19. according to the described method of arbitrary claim in the claim 1 to 18, wherein said GPR119 agonist is human GPR119 agonist.

20. according to the described method of arbitrary claim in the claim 1 to 19, wherein said GPR119 agonist is a micromolecule.

21. according to the described method of arbitrary claim in the claim 1 to 20, wherein said GPR119 agonist has the EC less than about 10 μ M ₅₀

22. the purposes of a GPR119 agonist, it is used to make for treatment or the individual medicine that is characterised in that the condition of illness of low bone mass of prevention.

23. purposes according to claim 22, the wherein said condition of illness that is characterised in that low bone mass is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.

24., wherein saidly be characterised in that the condition of illness of low bone mass is osteoporosis according to claim 22 or 23 described purposes.

25. the purposes of a GPR119 agonist, it is used to make the medicine for increasing individual bone mass.

26. purposes according to claim 25, the bmd of wherein said individuality (BMD) be lower than Young Adults with reference to the amount of meansigma methods greater than 1 standard deviation (T-scoring＜-1).

27. the purposes of a GPR119 agonist, it is used to make the medicine for the individual fracture of treatment.

28. purposes according to claim 27, wherein said fracture be traumatic fracture, for a long time the fracture or osteoporotic fracture.

29. the purposes of a GPR119 agonist, it is used to make the medicine for the individual osteopathia of treatment.

30. being selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer, purposes according to claim 29, wherein said osteopathia reduce the group that forms.

31. according to claim 29 or 30 described purposes, wherein said osteopathia is an osteoporosis.

32. the purposes of a GPR119 agonist, its be used to make for strengthen knitting after individual face reconstructions, upper jaw bone reconstructions, mandibular bone reconstruction, periodontal disease or the exodontia, strengthen the long bone extension, the enhancing restoration is inwardly grown or increase synestotic medicine.

33. according to the described purposes of arbitrary claim in the claim 22 to 32, wherein said GPR119 agonist is that the amount with the GIP content that is enough to increase described individuality provides.

34. according to the described purposes of arbitrary claim in the claim 22 to 33, wherein said individuality is human.

35. according to the described purposes of arbitrary claim in the claim 22 to 34, wherein said GPR119 agonist is human GPR119 agonist.

36. according to the described purposes of arbitrary claim in the claim 22 to 35, wherein said GPR119 agonist is a micromolecule.

37. according to the described purposes of arbitrary claim in the claim 22 to 36, wherein said GPR119 agonist has the EC50 less than about 10 μ M.

38. a method for the treatment of or preventing the condition of illness that is characterised in that low bone mass, it comprises to the individuality that needs are arranged throws and the GPR119 agonist and the DPP-IV inhibitor for the treatment of effective dose.

39. method for the treatment of or preventing the condition of illness that is characterised in that low bone mass, it comprises to the individuality that needs are arranged throws and the medical composition for the treatment of effective dose, and described medical composition comprises GPR119 agonist and DPP-IV inhibitor and pharmaceutically acceptable supporting agent.

40. according to claim 38 or 39 described methods, the wherein said condition of illness that is characterised in that low bone mass is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.

41., wherein saidly be characterised in that the condition of illness of low bone mass is osteoporosis according to claim 38 or 39 described method or purposes.

42. a method that increases bone mass, it comprises to the individuality that needs are arranged throws and the GPR119 agonist and the DPP-IV inhibitor for the treatment of effective dose.

43. a method that increases bone mass, it comprises to the individuality that needs are arranged throws and the medical composition for the treatment of effective dose, and described medical composition comprises GPR119 agonist and DPP-IV inhibitor and pharmaceutically acceptable supporting agent.

44. according to claim 42 or 43 described methods, the bmd of wherein said individuality (BMD) be lower than Young Adults with reference to the amount of meansigma methods greater than 1 standard deviation (T-scoring＜-1).

45. a method for the treatment of fracture, it comprises to the individuality that needs are arranged throws and the GPR119 agonist and the DPP-IV inhibitor for the treatment of effective dose.

46. a method for the treatment of fracture, it comprises to the individuality that needs are arranged throws and the medical composition for the treatment of effective dose, and described medical composition comprises GPR119 agonist and DPP-IV inhibitor and pharmaceutically acceptable supporting agent.

47. according to claim 45 or 46 described methods, wherein said individuality have traumatic fracture, for a long time the fracture or osteoporotic fracture.

48. a method for the treatment of osteopathia, it comprises to the individuality that needs are arranged throws and the GPR119 agonist and the DPP-IV inhibitor for the treatment of effective dose.

49. a method for the treatment of osteopathia, it comprises to the individuality that needs are arranged throws and the medical composition for the treatment of effective dose, and described medical composition comprises GPR119 agonist and DPP-IV inhibitor and pharmaceutically acceptable supporting agent.

50. according to claim 48 or 49 described methods, wherein said osteopathia is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.

51. according to claim 48 or 49 described methods, wherein said osteopathia is an osteoporosis.

52. one kind strengthens knitting after facial reconstructions, upper jaw bone reconstructions, mandibular bone reconstruction, periodontal disease or the exodontia, strengthens long bone and extend, strengthen restoration and inwardly grow or increase synestotic method, it comprises to the individuality throwing that needs are arranged and treats the GPR119 agonist and the DPP-IV inhibitor of effective dose.

53. one kind strengthen knitting after facial reconstructions, upper jaw bone reconstructions, mandibular bone reconstruction, periodontal disease or the exodontia, strengthen the long bone extension, the enhancing restoration is inwardly grown or increase synestotic method, it comprises to the individuality that needs are arranged throws and the medical composition for the treatment of effective dose, and described medical composition comprises GPR119 agonist and DPP-IV inhibitor and pharmaceutically acceptable supporting agent.

54. according to the described method of arbitrary claim in the claim 38 to 53, wherein said GPR119 agonist and described DPP-IV inhibitor be with the amount of the GIP content that is enough to increase described individuality throw with.

55. according to the described method of arbitrary claim in the claim 38 to 54, wherein said individuality is human.

56. according to the described method of arbitrary claim in the claim 38 to 55, wherein said GPR119 agonist is that human GPR119 agonist and/or described DPP-IV inhibitor are human DPP-IV inhibitor.

57. according to the described method of arbitrary claim in the claim 38 to 56, wherein said GPR119 agonist is that micromolecule and/or described DPP-IV inhibitor are micromolecule.

58. according to the described method of arbitrary claim in the claim 38 to 57, wherein said GPR119 agonist has the EC less than about 10 μ M ₅₀And/or described DPP-IV inhibitor has IC less than about 10 μ M ₅₀

59. the purposes of GPR119 agonist and DPP-IV inhibitor, it is used to make for treatment or the individual medicine that is characterised in that the condition of illness of low bone mass of prevention.

60. according to the described purposes of claim 59, the wherein said condition of illness that is characterised in that low bone mass is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.

61 according to claim 59 or 60 described purposes, wherein saidly are characterised in that the condition of illness of low bone mass is osteoporosis.

62. the purposes of GPR119 agonist and DPP-IV inhibitor, it is used to make the medicine that is used to increase individual bone mass.

63. according to the described purposes of claim 62, the bmd of wherein said individuality (BMD) be lower than Young Adults with reference to the amount of meansigma methods greater than 1 standard deviation (T-scoring＜-1).

64. the purposes of GPR119 agonist and DPP-IV inhibitor, it is used to make the medicine for the individual fracture of treatment.

65. according to the described purposes of claim 64, wherein said fracture be traumatic fracture, for a long time the fracture or osteoporotic fracture.

66. the purposes of GPR119 agonist and DPP-IV inhibitor, it is used to make the medicine for the individual osteopathia of treatment.

67. according to the described purposes of claim 66, wherein said osteopathia is selected from by osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone forfeiture, the forfeiture of osteotomy bone, the forfeiture of child Te Fa bone, handkerchief wise man bone forfeiture, osteolytic lesion, rachiocamposis and height sick, that cause because of metastatic cancer and reduces the group that forms.

68. according to claim 66 or 67 described purposes, wherein said osteopathia is an osteoporosis.

69. the purposes of GPR119 agonist and DPP-IV inhibitor, its be used to make for strengthen knitting after individual face reconstructions, upper jaw bone reconstructions, mandibular bone reconstruction, periodontal disease or the exodontia, strengthen the long bone extension, the enhancing restoration is inwardly grown or increase synestotic medicine.

70. according to the described purposes of arbitrary claim in the claim 59 to 69, wherein said GPR119 agonist and described DPP-IV inhibitor are that the amount with the GIP content that is enough to increase described individuality provides.

71. according to the described purposes of arbitrary claim in the claim 59 to 70, wherein said individuality is human.

72. according to the described purposes of arbitrary claim in the claim 59 to 71, wherein said GPR119 agonist is that human GPR119 agonist and/or described DPP-IV inhibitor are human DPP-IV inhibitor.

73. according to the described purposes of arbitrary claim in the claim 59 to 72, wherein said GPR119 agonist is that micromolecule and/or described DPP-IV inhibitor are micromolecule.

74. according to the described purposes of arbitrary claim in the claim 59 to 73, wherein said GPR119 agonist has the EC less than about 10 μ M ₅₀And/or described DPP-IV inhibitor has IC less than about 10 μ M ₅₀